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Overexpression of c-met in oral SCC promotes hepatocyte growth factor-induced disruption of cadherin junctions and invasion.
Int J Oncol. 2004 Oct; 25(4):831-40.IJ

Abstract

Hepatocyte growth factor (HGF), the ligand for the c-met proto-oncogene product, is a multifunctional protein that enhances tumor cell motility, extracellular matrix invasion, and mitogenic or morphogenic activities of various cell types. In this study we examined the expression of the c-Met receptor in human oral squamous cell carcinoma (SCC) in vivo and in vitro to explore its relationship to tumor progression and invasiveness. Biopsy specimens of human oral SCC were immunohistochemically stained for c-Met. Nearly all primary oral SCC lesions and lymph node metastases consistently showed intense staining for c-Met, whereas normal oral mucosa showed faint to negative staining only on basal cells. In a panel of human oral SCC cell lines, we found a strong correlation between the levels of c-Met expression and the cells' response to HGF in motility and invasion assays. Sensitivity to HGF also correlated with the expression of the c-Met 9-kb mRNA. When the non-invasive HOC-605 cell line, which expresses a low level of c-Met receptor, was transfected with an expression plasmid containing human c-met cDNA, the transfectant cells showed motile and invasive responses to HGF. Immunostaining and immunoprecipitation studies demonstrated that E-cadherin and c-Met were physically associated at SCC cell-cell junctions, suggesting a direct role for c-Met in induction of junctional integrity. Importantly, HGF caused a rapid elevation of unbound beta-catenin, suggesting its availability for nuclear signal transduction and triggering of cell motility and invasiveness. Thus, overexpression of c-Met may facilitate disruption of E-cadherin junctions. Collectively, these results suggest that HGF/c-Met signaling is a common event in oral SCC that may trigger phenotype modulation and enhanced invasion and metastasis.

Authors+Show Affiliations

Department of Stomatology, University of California San Francisco, San Francisco, CA 94143, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

15375530

Citation

Murai, M, et al. "Overexpression of C-met in Oral SCC Promotes Hepatocyte Growth Factor-induced Disruption of Cadherin Junctions and Invasion." International Journal of Oncology, vol. 25, no. 4, 2004, pp. 831-40.
Murai M, Shen X, Huang L, et al. Overexpression of c-met in oral SCC promotes hepatocyte growth factor-induced disruption of cadherin junctions and invasion. Int J Oncol. 2004;25(4):831-40.
Murai, M., Shen, X., Huang, L., Carpenter, W. M., Lin, C. S., Silverman, S., Regezi, J., & Kramer, R. H. (2004). Overexpression of c-met in oral SCC promotes hepatocyte growth factor-induced disruption of cadherin junctions and invasion. International Journal of Oncology, 25(4), 831-40.
Murai M, et al. Overexpression of C-met in Oral SCC Promotes Hepatocyte Growth Factor-induced Disruption of Cadherin Junctions and Invasion. Int J Oncol. 2004;25(4):831-40. PubMed PMID: 15375530.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Overexpression of c-met in oral SCC promotes hepatocyte growth factor-induced disruption of cadherin junctions and invasion. AU - Murai,M, AU - Shen,X, AU - Huang,L, AU - Carpenter,W M, AU - Lin,C S, AU - Silverman,S, AU - Regezi,J, AU - Kramer,R H, PY - 2004/9/18/pubmed PY - 2005/2/11/medline PY - 2004/9/18/entrez SP - 831 EP - 40 JF - International journal of oncology JO - Int. J. Oncol. VL - 25 IS - 4 N2 - Hepatocyte growth factor (HGF), the ligand for the c-met proto-oncogene product, is a multifunctional protein that enhances tumor cell motility, extracellular matrix invasion, and mitogenic or morphogenic activities of various cell types. In this study we examined the expression of the c-Met receptor in human oral squamous cell carcinoma (SCC) in vivo and in vitro to explore its relationship to tumor progression and invasiveness. Biopsy specimens of human oral SCC were immunohistochemically stained for c-Met. Nearly all primary oral SCC lesions and lymph node metastases consistently showed intense staining for c-Met, whereas normal oral mucosa showed faint to negative staining only on basal cells. In a panel of human oral SCC cell lines, we found a strong correlation between the levels of c-Met expression and the cells' response to HGF in motility and invasion assays. Sensitivity to HGF also correlated with the expression of the c-Met 9-kb mRNA. When the non-invasive HOC-605 cell line, which expresses a low level of c-Met receptor, was transfected with an expression plasmid containing human c-met cDNA, the transfectant cells showed motile and invasive responses to HGF. Immunostaining and immunoprecipitation studies demonstrated that E-cadherin and c-Met were physically associated at SCC cell-cell junctions, suggesting a direct role for c-Met in induction of junctional integrity. Importantly, HGF caused a rapid elevation of unbound beta-catenin, suggesting its availability for nuclear signal transduction and triggering of cell motility and invasiveness. Thus, overexpression of c-Met may facilitate disruption of E-cadherin junctions. Collectively, these results suggest that HGF/c-Met signaling is a common event in oral SCC that may trigger phenotype modulation and enhanced invasion and metastasis. SN - 1019-6439 UR - https://www.unboundmedicine.com/medline/citation/15375530/Overexpression_of_c_met_in_oral_SCC_promotes_hepatocyte_growth_factor_induced_disruption_of_cadherin_junctions_and_invasion_ L2 - http://www.spandidos-publications.com/ijo/25/4/831 DB - PRIME DP - Unbound Medicine ER -