Scatter-factor and semaphorin receptors: cell signalling for invasive growth
Nature reviews. CancerPublished 1 April 2002
Livio Trusolino, Paolo M. Comoglio
Citations739
SJR quartileQ1
SJR score24.38
SNIP11.13
Generate an AI Snapshot to get a quick, structured summary of this paper.
Study Snapshot
ObjectiveStudy objective
MethodsResearch methodology
PopulationPopulation studied
Sample sizeSample sizes
OutcomesStudy outcomes here
ResultsStudy results comes here
LimitationsResearch study limitations comes here
A concise AI-generated summary of the paper will appear here once you click Generate AI Snapshot.
TL;DR
This work investigates the role of scatter factors and semaphorins in neoplastic disease, and their role in the aberrant counterpart of a physiological programme for organ regeneration and maintenance.
Abstract
Malignant disease occurs when neoplastic cells abandon their primary site of accretion, cross tissue boundaries and penetrate the vasculature to colonize distant sites. This process --metastasis--is the aberrant counterpart of a physiological programme for organ regeneration and maintenance. Scatter factors and semaphorins, together with their receptors, help to orchestrate this programme. What are the differences between physiological and pathological activation of these signalling molecules, and can we exploit them therapeutically to prevent metastasis?
Keywords
MedicineNeuroscienceBiochemistry, Genetics and Molecular Biology
CellThe Hallmarks of Cancer
28,537 Citations2000Douglas Hanahan, Robert A. Weinberg
This work has been supported by the Department of the Army and the National Institutes of Health, and the author acknowledges the support and encouragement of the National Cancer Institute.
CellCell Signaling by Receptor Tyrosine Kinases
7,876 Citations2010Mark A. Lemmon, Joseph Schlessinger
Understanding of the complex signaling networks downstream from RTKs and how alterations in these networks are translated into cellular responses provides an important context for therapeutically countering the effects of pathogenic RTK mutations in cancer and other diseases.
Nature MedicineMechanisms of angiogenesis and arteriogenesis
4,114 Citations2000Peter Carmeliet
The cellular and molecular mechanisms underlying the formation of endothelium-lined channels and their maturation via recruitment of smooth muscle cells (arteriogenesis) during physiological and pathological conditions are summarized, alongside with possible therapeutic applications.
CellCell Signaling by Receptor Tyrosine Kinases
3,737 Citations2000Joseph Schlessinger
Receptor dimerization is of most fundamental cellular processes including the further stabilized by additional receptor:receptor inter-cell cycle, cell migration, cell metabolism and survival, actions.
NatureProliferation, cell cycle and apoptosis in cancer
3,400 Citations2001Gérard I. Evan, Karen H. Vousden
Deregulated cell proliferation provides a minimal 'platform' necessary to support further neoplastic progression and should be targeted withroit targeting to have potent and specific therapeutic consequences.
NatureMolecular cloning and expression of human hepatocyte growth factor
2,179 Citations1989Toshikazu Nakamura, Tsutomu Nishizawa +6 more
The nucleotide sequence of the human HGF cDNA reveals that both α- andβ-chains are contained in a single open reading frame coding for a pre-pro precursor protein of 728 amino acids, which indicates that the activity of HGF is not species-specific.
Nature reviews. CancerPutting tumours in context
2,167 Citations2001Mina J. Bissell, Derek C. Radisky
Investigation of the functional association of cancer cells with their surrounding tissues forms a new 'organ' that changes as malignancy progresses might provide new insights into the mechanisms of tumorigenesis and could also lead to new therapeutic targets.
CellLocalization of Matrix Metalloproteinase MMP-2 to the Surface of Invasive Cells by Interaction with Integrin αvβ3
1,546 Citations1996Peter C. Brooks, Staffan Strömblad +6 more
These findings define a single cell-surface receptor that regulates both matrix degradation and motility, thereby facilitating directed cellular invasion.
Nature GeneticsGermline and somatic mutations in the tyrosine kinase domain of the MET proto-oncogene in papillary renal carcinomas
1,532 Citations1997Laura S. Schmidt, Fuh-Mei Duh +33 more
NatureScatter factor/hepatocyte growth factor is essential for liver development
1,398 Citations1995Claudia Schmidt, Friedhelm Bladt +6 more
It is reported that mice lacking SF/HGF fail to complete development and die in utero, and the mutation affects the embryonic liver, which is reduced in size and shows extensive loss of parenchymal cells.
The Journal of Cell BiologyHepatocyte growth factor is a potent angiogenic factor which stimulates endothelial cell motility and growth.
1,353 Citations1992Federico Bussolino, Maria Flavia Di Renzo +8 more
Data show that HGF is an in vivo potent angiogenic factor and in vitro induces endothelial cells to proliferate and migrate and lacks activities related to hemostasis-thrombosis, inflammation and endothelium cells accessory functions.
Journal of Biological ChemistryLigand Binding to Integrins
1,341 Citations2000Edward F. Plow, Thomas A. Haas +3 more
The number of integrins and the remarkable breadth of their cellular distribution support the statement that the phenotype of virtually every cell is uniquely influenced by its display ofintegrins.
NatureScatter factor is a fibroblast-derived modulator of epithelial cell mobility
1,328 Citations1987M. G. P. Stoker, Ermanno Gherardi +2 more
The scatter factor is a paracrine effector of epithelial-mesenchymal interaction, which affects the intercellular connections and mobility of normal epithelial cells, and might be involved in epithelial migration.
NatureEssential role for the c-met receptor in the migration of myogenic precursor cells into the limb bud
1,282 Citations1995Friedhelm Bladt, Dieter Riethmacher +3 more
It is reported that the c-met-encoded receptor tyrosine kinase is essential for migration of myogenic precursor cells into the limb anlage and for migration into diaphragm and tip of tongue.
ScienceInduction of Cell Migration by Matrix Metalloprotease-2 Cleavage of Laminin-5
1,218 Citations1997Gianluigi Giannelli, Jutta Falk-Marzillier +3 more
Cleavage of laminin-5 by MMP2 and the resulting activation of the Ln-5 cryptic site may provide new targets for modulation of tumor cell invasion and tissue remodeling.
Current Opinion in Cell BiologyAnoikis mechanisms
1,199 Citations2001Steven M. Frisch, Robert A. Screaton
Anoikis is defined as apoptosis that is induced by inadequate or inappropriate cell-matrix interactions and the initiation of the caspase cascade remains to be explained.
CellCollapsin: A protein in brain that induces the collapse and paralysis of neuronal growth cones
1,181 Citations1993Yuling Luo, David W. Raible +1 more
It is proposed that collapsin could serve as a ligand that guides specific growth cones by a motility-inhibiting mechanism.
CellIdentification of a fibroblast-derived epithelial morphogen as hepatocyte growth factor
1,159 Citations1991Roberto Montesano, Kunio Matsumoto +2 more
The results demonstrate that HGF, a polypeptide that was identified as a mitogen for cultured hepatocytes, has the properties of a paracrine mediator of epithelial morphogenesis, and suggest that it may play important roles in the formation of parenchymal organs during embryonic development.
CellPlexins Are a Large Family of Receptors for Transmembrane, Secreted, and GPI-Anchored Semaphorins in Vertebrates
1,157 Citations1999Luca Tamagnone, Stefania Artigiani +10 more
It is concluded that plexins are receptors for multiple (and perhaps all) classes of semaphorins, either alone or in combination with neuropilins, and trigger a novel signal transduction pathway controlling cell repulsion.
NaturePlacental defect and embryonic lethality in mice lacking hepatocyte growth factor/scatter factor
1,040 Citations1995Yoshihiko Uehara, Osamu Minowa +5 more
CellA multifunctional docking site mediates signaling and transformation by the hepatocyte growth factor/scatter factor receptor family
991 Citations1994Carola Ponzetto, Alberto Bardelli +7 more
The existence in the hepatocyte growth factor/scatter factor (HGF/SF) receptor of a multifunctional docking site made of the tandemly arranged degenerate sequence YVH/NV is reported, suggesting that in all members of the HGF/ SF receptor family, signal transduction is channeled through a multifunctionsal binding site.
Nature reviews. NeuroscienceRHO GTPASES in neuronal morphogenesis
985 Citations2000Liqun Luo
The Rho family of small GTPases act as intracellular molecular switches that transduce signals from extracellular stimuli to the actin cytoskeleton and the nucleus, underscoring their importance in the development and function of the nervous system.
NatureMolecular cloning of a new transforming gene from a chemically transformed human cell line
985 Citations1984Colin S. Cooper, Morag Park +5 more
Molecular cloning of the transforming gene from a chemically transformed human osteosarcoma-derived cell line enables the gene to be mapped to chromosome 7 (7p11.4–7qter) and by direct hybridization to be shown to be unrelated to known oncogenes.
CellThe semaphorin genes encode a family of transmembrane and secreted growth cone guidance molecules
957 Citations1993Alex L. Kolodkin, David Matthes +1 more
The cloning and characterization of two sema genes in Drosophila, one in human, and the identification of two related viral sequences are reported, all of which encode proteins with conserved Semaphorin domains.
NatureSemaphorin 3A is a chemoattractant for cortical apical dendrites
686 Citations2000Franck Polleux, Theresa Morrow +1 more
The EMBO JournalScatter factor and hepatocyte growth factor are indistinguishable ligands for the MET receptor.
667 Citations1991Luigi Naldini, K. Michael Weidner +8 more
It is concluded that the same molecule (SF/HGF), purified according to their respective biological activities, acts as a growth or motility factor through a single receptor in different target cells.
Nature MedicineHepatocyte growth factor gene therapy of liver cirrhosis in rats
585 Citations1999Takahiro Ueki, Yasufumi Kaneda +9 more
In a rat model of lethal liver cirrhosis produced by dimethylnitrosamine administrations, repeated transfections of the human HGF gene into skeletal muscles induced a high plasma level of human as well as enodogenous rat HGF, and tyrosine phosphorylation of the c–Met/HGF receptor suppressed the increase of transforming growth factor–β1 and produced the complete resolution of fibrosis in the cirrhotic liver.
NatureInteraction between Gab1 and the c-Met receptor tyrosine kinase is responsible for epithelial morphogenesis
578 Citations1996K. Michael Weidner, Silvana Di Cesare +4 more
A new phosphotyrosine interaction domain is discovered in Gab1 and it is shown that Gab1 is the substrate of the c-Met receptor tyrosine kinase that mediates epithelial morphogenesis.
NatureInduction of epithelial tubules by growth factor HGF depends on the STAT pathway
524 Citations1998Carla Boccaccio, Margherita Andò +5 more
Electroporation of a tyrosine-phosphorylated peptide, which interferes with both the association of STAT to the receptor and STAT dimerization, inhibits tubule formation in vitro without affecting either HGF-induced ‘scattering' or growth.
OncogeneNovel mutations of the MET proto-oncogene in papillary renal carcinomas
505 Citations1999Laura S. Schmidt, Kerstin Junker +17 more
The low frequency of MET mutations in noninherited papillary renal carcinomas (PRC) suggests that non inherited PRC may develop by a different mechanism than hereditary papillary kidneys carcinoma.
CellInduction of epithelial tubular morphogenesis in vitro by fibroblast-derived soluble factors
490 Citations1991Roberto Montesano, G. Eric Schaller +1 more
Evidence that fibroblast-derived soluble factors play a crucial role in the control of epithelial morphogenesis is obtained and the involvement of diffusible paracrine factors in morphogenetic epithelial-mesenchymal interactions is demonstrated and a strategy for their molecular characterization is provided.
NatureTyrosine kinase receptor indistinguishable from the c-met protein
487 Citations1989Silvia Giordano, Carola Ponzetto +3 more
It is shown that p190 is indistinguishable from the protein encoded by the c-met protooncogene and that the αβ-subunit structure is conserved in other human cell lines, and the high level of p190 found in the GTL-16 cell line is accompanied by amplification and overexpression of c- Met.
NatureThe endophilin–CIN85–Cbl complex mediates ligand-dependent downregulation of c-Met
476 Citations2002Annalisa Petrelli, Giorgio F. Gilestro +4 more
Inhibition of complex formation is sufficient to block HGF receptor internalization and to enhance HGF-induced signal transduction and biological responses, and disclose a novel functional role for Cbl in HGF receptors signalling.
CellPlexin A Is a Neuronal Semaphorin Receptor that Controls Axon Guidance
470 Citations1998Margaret L. Winberg, Jasprina N. Noordermeer +5 more
Two Drosophila Plexins are identified and evidence that Plexin A is a neuronal receptor for class I Semaphorins (Sema 1a and Sema 1b) is presented and it is shown thatPlexin A controls motor and CNS axon guidance.
The Journal of Cell BiologyNeuropilin-1 Mediates Collapsin-1/Semaphorin III Inhibition of Endothelial Cell Motility
463 Citations1999Hua‐Quan Miao, Shay Söker +4 more
Results suggest that collapsin-1 can inhibit EC motility as well as axon motility, that these inhibitory effects on motility are mediated by NRP1, and that VEGF165 and collaps in-1 compete for NRP 1-binding sites.
PubMedOverexpression and amplification of the met/HGF receptor gene during the progression of colorectal cancer.
456 Citations1995Maria Flavia Di Renzo, Martina Olivero +8 more
Overexpression of the c-met oncogene contributes a selective growth advantage to neoplastic colorectal cells at any stage of tumor progression and amplification appears to give a further selective advantage for the acquisition of metastatic potential.
Molecular CellMutation of the c-Cbl TKB Domain Binding Site on the Met Receptor Tyrosine Kinase Converts It into a Transforming Protein
451 Citations2001Pascal Peschard, Tanya M. Fournier +5 more
It is shown that c-Cbl promotes ubiquitination of the Met RTK, a Met receptor where the juxtamembrane tyrosine is replaced by phenylalanine, is not ubiquitinated and has transforming activity in fibroblast and epithelial cells.
Proceedings of the National Academy of SciencesGene expression in papillary thyroid carcinoma reveals highly consistent profiles
448 Citations2001Ying Huang, Manju L. Prasad +10 more
Papillary thyroid carcinoma is characterized by consistent and specific molecular changes, which reveal clues to the molecular pathways involved in PTC and may provide biomarkers for clinical use.
CellUnified Nomenclature for the Semaphorins/Collapsins
447 Citations1999CS Goodman, Alex L. Kolodkin +3 more
A new semaphorin is defined as a fully sequenced gene, cDNA, or protein which by sequence homology falls into the semaphOrin family of proteins.
Proceedings of the National Academy of SciencesActivating mutations for the Met tyrosine kinase receptor in human cancer
440 Citations1997Michael Jeffers, Laura S. Schmidt +6 more
The results demonstrate that the Met mutants originally identified in human papillary renal carcinoma are oncogenic and thus are likely to play a determinant role in this disease, and raise the possibility that activating Met mutations also may contribute to other human malignancies.
Proceedings of the National Academy of SciencesDiverse tumorigenesis associated with aberrant development in mice overexpressing hepatocyte growth factor/scatter factor
439 Citations1997Hisashi Takayama, William J. LaRochelle +6 more
Subversion of normal mesenchymal-epithelial paracrine regulation through the forced misdirection of HGF/SF expression induces aberrant morphogenesis and subsequent malignant transformation of cells of diverse origin.
CellA Signaling Adapter Function for α6β4 Integrin in the Control of HGF-Dependent Invasive Growth
417 Citations2001Livio Trusolino, Andrea Bertotti +1 more
It is demonstrated here that Met selectively associates with alpha6beta4, generating an additional signaling platform that potentiates HGF-triggered activation of Ras- and PI3K-dependent pathways.
Cell adhesion and communications/Cell adhesion and communication/Cell adhesion & communicationTyrosine Phosphorylation of β-Catenin and Plakoglobin Enhanced by Hepatocyte Growth Factor and Epidermal Growth Factor in Human Carcinoma Cells
416 Citations1994Sayumi Shibamoto, Makio Hayakawa +7 more
The results suggest that HGF/SF and EGF may modulate the function of the cadherin-catenin system via tyrosine phosphorylation of cadhersin-associated proteins.
Proceedings of the National Academy of SciencesHepatocyte growth factor prevents acute renal failure and accelerates renal regeneration in mice.
410 Citations1994Kouichi Kawaida, Kunio Matsumoto +2 more
Intravenous injection of recombinant human HGF into mice remarkably suppressed increases in blood urea nitrogen and serum creatinine caused by administration of cisplatin, a widely used antitumor drug, or HgCl2, thereby indicating that HGF strongly prevented the onset of acute renal dysfunction.
NeuronHepatocyte Growth Factor/Scatter Factor Is an Axonal Chemoattractant and a Neurotrophic Factor for Spinal Motor Neurons
401 Citations1996Allen Ebens, Katja Brose +6 more
Results indicate that, in addition to functioning as a mitogen, a motogen, and a morphogen in nonneural systems, HGF/SF can function as a guidance and survival factor in the developing nervous system.
Proceedings of the National Academy of SciencesInvasiveness and metastasis of NIH 3T3 cells induced by Met-hepatocyte growth factor/scatter factor autocrine stimulation.
365 Citations1994Sing Rong, Shoshana Segal +3 more
It is shown that Metmu and HMH cells are invasive in vitro and display enhanced protease activity necessary for the invasive phenotype and autocrine-mediated Met-HGF/SF signal transduction in NIH 3T3 mesenchymal cells may provide an important system for understanding the biological process of metastasis.
Current Opinion in NeurobiologyRho GTPases in growth cone guidance
361 Citations2001Barry J. Dickson
The growth cone is guided by signals transduced both via and independently of Rho GTPases, and this work has provided the first strong evidence for an instructive role.
Trends in Cell BiologySignalling by semaphorin receptors: cell guidance and beyond
352 Citations2000Luca Tamagnone, Paolo M. Comoglio
This work has shown that plexins, alone, or in association with neuropilins, behave as fully functional semaphorin receptors, and their large cytoplasmic moiety is likely to trigger novel signal-transduction pathways.
Nature NeuroscienceDynamic regulation of axon guidance
346 Citations2001Timothy W. Yu, Cornelia I. Bargmann
The mechanisms by which a few guidance systems can be used to generate diverse outcomes are considered, as well as combinatorial mechanisms that integrate information from different families of guidance cues.
The Journal of Cell BiologyCoupling of Gab1 to C-Met, Grb2, and Shp2 Mediates Biological Responses
343 Citations2000Ute Schaeper, Niels H. Gehring +4 more
To detect phosphorylation-dependent interactions of Gab1 with downstream substrates, a modified yeast two-hybrid assay was developed and identified PI(3)K, Shc, Shp2, and CRKL as interaction partners of Gab 1.
PubMedHepatocyte growth factor and its receptor (c-MET) in prostatic carcinoma.
332 Citations1995Peter A. Humphrey, Xiaopei Zhu +5 more
Data indicate that HGF may function in the prostate gland as a paracrine growth factor, with synthesis by stromal cells and with biological target cells being the epithelial cells, and the effect of purified recombinant HGF on cell proliferation and scattering of prostatic carcinoma cell lines is determined.
OncogeneSomatic mutations of the MET oncogene are selected during metastatic spread of human HNSC carcinomas
330 Citations2000Maria Flavia Di Renzo, Martina Olivero +8 more
Data indicate that cells expressing mutant MET undergo clonal expansion during HNSCC progression and suggest that MET might be one of the long sought oncogenes controlling progression of primary cancers to metastasis.
OncogeneA novel germ line juxtamembrane Met mutation in human gastric cancer
327 Citations2000Jae‐Ho Lee, San-Uk Han +7 more
A novel germline missense Met mutation is reported, P1009S, in a patient with primary gastric cancer, where the dosage of the mutant Met DNA was elevated in the tumor when compared to its matched normal DNA.
PubMedOverexpression of the c-MET/HGF receptor gene in human thyroid carcinomas.
318 Citations1992Maria Flavia Di Renzo, Martina Olivero +8 more
A role for the overexpression of c-MET oncogene in the pathogenesis and progression of thyroid tumors derived from the follicular epithelium is suggested.
CellUncoupling of Grb2 from the Met Receptor In Vivo Reveals Complex Roles in Muscle Development
307 Citations1996Flavio Maina, Franca Casagranda +5 more
The data show that the requirements for Met signaling vary depending on the tissue and reveal a novel role for HGF/ Met in late myogenesis, as well as highlighting the importance of knowing the carrier and removal status of canine coronavirus.
The EMBO JournalRON is a heterodimeric tyrosine kinase receptor activated by the HGF homologue MSP.
307 Citations1994Giovanni Gaudino, Antonia Follenzi +6 more
The data show that p185RON is a tyrosine kinase activated by MSP and that it is member of a family of growth factor receptors with distinct specificities for structurally related ligands.
The Journal of Cell BiologyHepatocyte growth factor/scatter factor induces a variety of tissue-specific morphogenic programs in epithelial cells.
300 Citations1995Volker Brinkmann, Hamid Reza Foroutan +3 more
Data show that HGF/SF induces intrinsic, tissue-specific morphogenic activities in a wide variety of epithelial cells, and is thus an inductive, not an instructive, mesenchymal effector for epithelial morphogenesis.
Current Opinion in Cell BiologyMolecular architecture of adherens junctions
296 Citations2001Akira Nagafuchi
Adherens junctions are composed of a cadherin-catenin complex and its associated proteins and their associated proteins, and interactions among these components seem to be dynamically regulated during the formation of ad herens junction complexes in epithelial cells.
The EMBO JournalStructure‐function analysis of hepatocyte growth factor: identification of variants that lack mitogenic activity yet retain high affinity receptor binding.
296 Citations1992Nathalie A. Lokker, Melanie R. Mark +5 more
The results show that single‐chain HGF is a zymogen‐like promitogen in that cleavage into a two‐chain form is required for biological activity, however, the single chain form of HGF still retains substantial receptor binding capacity.
PubMedThe Met/HGF receptor is over-expressed in human osteosarcomas and is activated by either a paracrine or an autocrine circuit.
284 Citations1995Riccardo Ferracini, Maria Flavia Di Renzo +7 more
Activation of the Met/HGF receptor by a paracrine or an autocrine mechanism might play a role in the particularly aggressive behaviour of osteosarcomas.
Molecular and Cellular BiologyThe Tyrosine Phosphatase SHP-2 Is Required for Sustained Activation of Extracellular Signal-Regulated Kinase and Epithelial Morphogenesis Downstream from the Met Receptor Tyrosine Kinase
284 Citations2000Christiane R. Maroun, Monica A. Naujokas +3 more
A structure-function approach is undertook and it is demonstrated that association of Gab1 with the tyrosine phosphatase SHP-2 is required for sustained Erk activation and for epithelial morphogenesis downstream from the Met receptor.
The Journal of Cell BiologyActivation of the Met Receptor by Cell Attachment Induces and Sustains Hepatocellular Carcinomas in Transgenic Mice
277 Citations2001Rong Wang, Linda D. Ferrell +3 more
It is shown that overexpression of the Met RTK allows activation of the receptor by cell attachment and that this form of activation can be tumorigenic, providing evidence that Met may play a role in both the genesis and maintenance of HCC, and suggesting thatMet may be a beneficial therapeutic target in tumors that overexpress the receptor.
PubMedC-Met Autocrine Activation Induces Development Of Malignant Melanoma And Acquisition Of The Metastatic Phenotype
269 Citations1998Toshiyuki Otsuka, Hisashi Takayama +9 more
Transgenic mice are used to show that the Met signaling pathway is an important in vivo regulator of melanocyte function, whose subversion induces malignant melanoma, and support a causal role for HGF/SF-Met signaling in the development of melanoma and acquisition of the metastatic phenotype.
PubMedExpression of the Met/hepatocyte growth factor receptor in human pancreatic cancer.
263 Citations1995Maria Flavia Di Renzo, Richard Poulsom +3 more
The c-MET oncogene encodes the receptor for hepatocyte growth factor (HGF) scatter factor, a multifunctional cytokine able to mediate morphogenesis as well as invasive growth of epithelial cells, which may contribute to the ductal phenotype of these tumors.
ScienceIdentification of the <i>ron</i> Gene Product as the Receptor for the Human Macrophage Stimulating Protein
260 Citations1994Ming‐Hai Wang, Christophe Ronsin +5 more
The ron gene product is established as a specific cell-surface receptor for MSP, causing phosphorylation of the beta chain of Ron and induced migration of MDCK-RE7 cells.
PubMedSomatic mutations in the kinase domain of the Met/hepatocyte growth factor receptor gene in childhood hepatocellular carcinomas.
253 Citations1999Won Sang Park, Seung Myung Dong +16 more
The results indicate that mutations of the tyrosine kinase domain of the MET gene may be involved in the acceleration of the carcinogenesis in childhood HCC.
PubMedCoexpression of hepatocyte growth factor and receptor (Met) in human breast carcinoma.
243 Citations1996Alan B. Tuck, M Park +3 more
The finding that HGFR is expressed by both benign and malignant epithelium, and its not restricted to duct-forming structures, suggests that, although the potential for HGF/HGFR binding is maintained in malignancy, the response to ligand binding at the level of the receptor or the cellular response to receptor activation may change at some point during progression.
Journal of Cell ScienceHepatocyte growth factor stimulates extensive development of branching duct-like structures by cloned mammary gland epithelial cells
232 Citations1995Jesús V. Soriano, Michael S. Pepper +3 more
It is demonstrated that hepatocyte growth factor promotes the formation of branching duct-like structures by mammary gland epithelial cells in vitro, and suggested that it may act as a mediator of the inducing effect of mesenchyme (or stroma) on mammary glands development.
Current Opinion in NeurobiologySequential steps in clathrin-mediated synaptic vesicle endocytosis
226 Citations2000Lennart Brodin, Péter Lőw +1 more
Protein perturbation studies in living nerve terminals are now beginning to link the actions of different 'accessory' proteins linked to this pathway with morphologically defined steps of endocytosis.
Proceedings of the National Academy of SciencesThe mutationally activated Met receptor mediates motility and metastasis
226 Citations1998Michael Jeffers, Michele Fiscella +4 more
It is found that mutant Met induces the motility of Madin-Darby canine kidney cells in vitro and experimental metastasis of NIH 3T3 cells in vivo, and that the Ras-Raf-MEK-ERK signaling pathway, which has been implicated previously in cellular motility and metastasis, is constitutively activated by the Met mutants.
Genes & DevelopmentMet receptor signaling is required for sensory nerve development and HGF promotes axonal growth and survival of sensory neurons
224 Citations1997Flavio Maina, Mark Hilton +3 more
Using in vitro assays, it is found that HGF cooperates with nerve growth factor (NGF) to enhance axonal outgrowth from cultured dorsal root ganglion neurons, and Met receptor signaling is required for the survival of a proportion of DRG neurons in vivo.
Proceedings of the National Academy of SciencesA functional domain in the heavy chain of scatter factor/hepatocyte growth factor binds the c-Met receptor and induces cell dissociation but not mitogenesis.
223 Citations1992Gunther Hartmann, Luigi Naldini +5 more
ScienceIdentification of a Competitive HGF Antagonist Encoded by an Alternative Transcript
220 Citations1991Andrew M. Chan, Jeffrey S. Rubin +4 more
A naturally occurring hepatocyte growth factor variant is identified, whose predicted sequence extends only through the second kringle domain of this plasminogen-related molecule, and cross-linking studies demonstrated that the truncated molecule competes with HGF for binding to the HGF receptor.
International Journal of CancerOverexpression of theMET/HGF receptor in ovarian cancer
214 Citations1994Maria Flavia Di Renzo, Martina Olivero +6 more
Data suggest that expression of the Met/HGF receptor may add a selective growth advantage to a narrow subset of differentiated ovarian cancers in premenopausal patients.
PubMedHGF/NK4, a four-kringle antagonist of hepatocyte growth factor, is an angiogenesis inhibitor that suppresses tumor growth and metastasis in mice.
214 Citations2000Keiji Kuba, Kunio Matsumoto +4 more
The first evidence is provided that NK4 inhibits tumor growth and metastasis as an angiogenesis inhibitor as well as an HGF antagonist, and that the antiangiogenic action of NK4 is independent of its activity as HGF antagonists.
Proceedings of the National Academy of SciencesNeutralizing monoclonal antibodies to hepatocyte growth factor/scatter factor (HGF/SF) display antitumor activity in animal models
214 Citations2001Brian Cao, Yanli Su +6 more
The results suggest interrupting autocrine and/or paracrine Met-HGF/SF signaling in tumors dependent on this pathway is a possible intervention strategy.
NeuronPlexin B Mediates Axon Guidance in Drosophila by Simultaneously Inhibiting Active Rac and Enhancing RhoA Signaling
205 Citations2001Hailan Hu, Tobias F. Marton +1 more
A model whereby PlexB mediates repulsion by coordinately regulating two small GTPases in opposite directions is suggested: PlexB binds to Rac(GTP) and downregulates its output by blocking its access to PAK and, at the same time, binds to and increases the output of RhoA.
American Journal of Respiratory and Critical Care MedicineSimultaneous or Delayed Administration of Hepatocyte Growth Factor Equally Represses the Fibrotic Changes in Murine Lung Injury Induced by Bleomycin
203 Citations1997Masahiro Yaekashiwa, Shoichi Nakayama +8 more
Exogenous HGF acts as a pulmotrophic factor in vivo and prevents the progression of BLM-induced lung injury when administered in either a simultaneous or delayed fashion, indicating that HGF may be a potent candidate to prevent or treat lung fibrosis.
FEBS LettersThe semaphorin 3A receptor may directly regulate the activity of small GTPases
187 Citations2000Beate Rohm, Belquis Rahim +3 more
The data suggest that plexins may be integral membrane proteins with an intrinsic GAP activity that is essential for their ability to induce growth cone collapse.
Current BiologyPlexin-B semaphorin receptors interact directly with active Rac and regulate the actin cytoskeleton by activating Rho
186 Citations2001M.H.E. Driessens, Hailan Hu +5 more
The findings that plexin-B signaling to the cytoskeleton is both Rac and Rho dependent form a starting point for unraveling the mechanism by which semaphorins and plexins control axon guidance and cell migration.
The FASEB JournalIn vivo targeting of SF/HGF and c‐met expression via U1snRNA/ribozymes inhibits glioma growth and angiogenesis and promotes apoptosis
185 Citations2001Roger Abounader, Bachchu Lal +5 more
PubMedThe motogenic and mitogenic responses to HGF are amplified by the Shc adaptor protein.
179 Citations1995Pier Giuseppe Pelicci, Silvia Giordano +8 more
Overexpression of wild-type Shc, but not of the Y317-->F mutant, enhances cell migration and growth in response to HGF, showing that Shc is a relevant substrate of the HGF receptor, and works as an 'amplifier' of the motogenic as well as of the mitogenic response.
PubMedc-met is amplified but not mutated in a cell line with an activated met tyrosine kinase.
174 Citations1991Carola Ponzetto, Silvia Giordano +5 more
It is suggested that the present c-met cDNA presumably reflects the sequence of the most abundant transcript in several cell types, and that over-expression of the normal c- Met protein, alone or in combination with an autocrine loop, is most probably responsible for the activation of the c-Met kinase in GTL-16 cells.
Proceedings of the National Academy of SciencesThe semaphorin receptor plexin-B1 specifically interacts with active Rac in a ligand-dependent manner
172 Citations2000Haris G. Vikis, Weiquan Li +2 more
The Journal of Experimental MedicineMacrophage stimulating protein: purification, partial amino acid sequence, and cellular activity.
169 Citations1991Alison Skeel, Teizo Yoshimura +4 more
MSP causes direct or indirect activation of two receptors of the mouse resident peritoneal macrophage, CR1 and the C5a receptor, and causes the appearance of long cytoplasmic processes and pinocytic vesicles in freshly plated macrophages.
PubMedMatrilysin mediates extracellular cleavage of E-cadherin from prostate cancer cells: a key mechanism in hepatocyte growth factor/scatter factor-induced cell-cell dissociation and in vitro invasion.
169 Citations2001G. Davies, Wen G. Jiang +1 more
Treatment with HGF/SF induced Matrilysin-mediated cleavage to the extracellular domain of E-cadherin, resulting in its dissociation from the cadherin/catenin complex, which provides a new mechanism in H GF/SF-induced cell scattering, causing a switch to a more invasive phenotype in LNCapFGC cells, as demonstrated by in vitro invasion.
PubMedCreation of an hepatocyte growth factor/scatter factor autocrine loop in carcinoma cells induces invasive properties associated with increased tumorigenicity.
169 Citations1994Savério Bellusci, G Moëns +5 more
Results show that HGF/SF can promote motility and invasive properties of NBT-II bladder carcinoma cells and also confers a tumorigenic advantage when acting as an autocrine factor.
NeuronThe Transmembrane Protein Off-Track Associates with Plexins and Functions Downstream of Semaphorin Signaling during Axon Guidance
168 Citations2001Margaret L. Winberg, Luca Tamagnone +4 more
Genetic and biochemical analysis in Drosophila is used to show that the transmembrane protein Off-track (OTK) associates with Plexin A, the receptor for Sema 1a, and that OTK is a component of the repulsive signaling response to Semaphorin ligands.
CINECA IRIS Institutial Research Information System (University of Genoa)THE MET/HGF RECEPTOR IS OVER-EXPRESSED IN HUMAN OSTEOSARCOMAS AND IS ACTIVATED BY EITHER A PARACRINE OR AN AUTOCRINE CIRCUIT
165 Citations1995FERRACINI, RICCARDO, DIRENZO MF +7 more
CancerExpression of scatter factor and c‐ <i>met</i> receptor in benign and malignant breast tissue
164 Citations1997Liang Jin, Alexander Fuchs +7 more
To investigate the possible involvement of SF and c‐met in the evolution of breast carcinoma, the authors studied their expression in sections of human breast tissue.
Journal of Cell ScienceBranching morphogenesis of human mammary epithelial cells in collagen gels
161 Citations1994Feodor Berdichevsky, Deborah Alford +2 more
The results suggest that the modulation of alpha 3 beta 1 activity may represent an important event in the induction of branching morphogenesis of human mammary epithelial cells.
CancerMet expression is associated with poor outcome in patients with axillary lymph node negative breast carcinoma
156 Citations1999Robert L. Camp, Eric B. Rimm +1 more
Activation of Met, the receptor for scatter factor/hepatocyte growth factor, is associated with mitogenesis, motogenesis, and decreased cell adhesion in patients with breast carcinoma.
OncogeneSustained recruitment of phospholipase C-γ to Gab1 is required for HGF-induced branching tubulogenesis
154 Citations2000Philippe Gual, Silvia Giordano +4 more
Sustained recruitment of PLCγ to Gab1 plays an important role in branching tubulogenesis and is concluded that sustained recruitment of HGF receptor directly activates PI3 kinase, Ras and STAT signalling pathways and phosphorylates the adaptator GRB2 Associated Binder-1.
DevelopmentHepatocyte growth factor (HGF/SF) is a muscle-derived survival factor for a subpopulation of embryonic motoneurons
151 Citations1997Yoichi Yamamoto, Jean Livet +5 more
It is shown that HGF/SF has potent neurotrophic activity (EC50=2 pM) for a subpopulation (40%) of purified embryonic rat motoneurons and may play an important role during motoneuron development as a muscle-derived survival factor for aSubpopulation of limb-innervating mot oneurons.
Cancer Genetics and CytogeneticsChanges in gene expression during progression of ovarian carcinoma
148 Citations2001Johanna Tapper, Eeva Kettunen +4 more
Differences were found in the gene expression between benign and malignant serous ovarian tumors, and between local, highly differentiated and advanced and/or moderately or poorly differentiated serous adenocarcinomas.
OncogeneDuplication and overexpression of the mutant allele of the MET proto-oncogene in multiple hereditary papillary renal cell tumours
148 Citations1998Joachim Fischer, Gabriele Palmedo +5 more
The lack of germline mutation in two members of another HPRT family and duplication of the same parental allele of chromosome 7 in multiple tumours suggests that a germ line event other than mutation of MET tyrosine kinase is involved in the development of these tumours.
PubMedTranscription of a novel mouse semaphorin gene, M-semaH, correlates with the metastatic ability of mouse tumor cell lines.
145 Citations1998Claus Christensen, Jörg Klingelhöfer +4 more
To the authors' knowledge, this is the first time that the expression of a semaphorin gene has been shown to correlate positively with tumor progression and characterized two transcripts present in the tumor cells.
Journal of NeuroscienceChemoattraction and Chemorepulsion of Olfactory Bulb Axons by Different Secreted Semaphorins
145 Citations1999Fernando de Castro, Ling‐Jia Hu +3 more
The expression patterns of sema A and sema IV in the developing olfactory system confirm that they may play a cooperative role in the formation of the lateral olfaction tract and represent a further evidence for a chemoattractive function of secreted semaphorins.
CellSignaling Networks—Do All Roads Lead to the Same Genes?
144 Citations1999Tony Pawson, Tracy M. Saxton
Oligonucleotide and cDNA arrays are clearly changing the ways the authors think about cell biology, and the paper by Fambrough et al. reveals both the power of this approach, and also their ignorance about cellular function.
…