Overexpression of c-met in oral SCC promotes hepatocyte growth factor-induced disruption of cadherin junctions and invasion

  • Authors:
    • M. Murai
    • X. Shen
    • L. Huang
    • W. M. Carpenter
    • C. S. Lin
    • S. Silverman
    • J. Regezi
    • R. H. Kramer
  • View Affiliations

  • Published online on: Friday, October 1, 2004
  • Pages: 831-840
  • DOI: 10.3892/ijo.25.4.831

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 β-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.
Journal Cover

October 2004
Volume 25 Issue 4

Print ISSN: 1019-6439
Online ISSN:1791-2423

2013 Impact Factor: 2.773
Ranked #30/202 Oncology
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APA
Murai, M., Shen, X., Huang, L., Carpenter, W., Lin, C., Silverman, S., Regezi, J., & Kramer, R. (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), 831-840.
MLA
Murai, Shen, Huang, Carpenter, Lin, Silverman, Regezi, and R. Kramer. "Overexpression of c-met in oral SCC promotes hepatocyte growth factor-induced disruption of cadherin junctions and invasion." International Journal of Oncology International Journal of Oncology 25.4 (2004): 831-840.
Chicago
Murai, Shen, Huang, Carpenter, Lin, Silverman, Regezi, and R. Kramer. "Overexpression of c-met in oral SCC promotes hepatocyte growth factor-induced disruption of cadherin junctions and invasion." International Journal of Oncology International Journal of Oncology 25 no. 4 (2004): 831-840.