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Sci. STKE, 11 December 2001
Vol. 2001, Issue 112, p. tw452
[DOI: 10.1126/stke.2001.112.tw452]

EDITORS' CHOICE

Cancer Biology α6β4 Integrin Leads the Invasion

The α6β4 integrin and the hepatocyte growth factor (HGF) receptor tyrosine kinase termed Met can participate in tumor invasion. However, Trusolino et al. have found that independent of α6β4's solitary effects on invasion, α6β4 participates in HGF- and Met-dependent invasion in a capacity not usually associated with integrins: as an adapter protein. In the absence of α6β4, HGF-dependent activation of Met in tumor cells did not induce cell invasion through a matrix, in vitro. HGF did stimulate invasion in cells expressing Met and α6β4, but treatment with β4-specific neutralizing antibodies (that block the association of β4-containing integrins to proteins in the extracellular matrix) did not inhibit invasion. In fact, in the same system, expression of a β4 deletion mutant that had no extracellular region did not decrease invasion, indicating that although α6β4 integrin was essential for invasion, this effect was not dependent on α6β4 binding to the extracellular matrix. HGF-dependent activation of Met (in the absence of α6β4) leads to the transduction of some downstream signaling; however, the presence of α6β4 led to the recruitment of the adapter protein SHC and phosphatidylinositol 3 kinase (PI3K), which amplified the Met-dependent activation of Ras and PI3K. Mutation of the sites on α6β4 required for SHC binding greatly reduced the activation of PI3K-mediated signal and Ras-mediated activation of the mitogen-associated protein kinases (MAPKs), suggesting that the function of α6β4 (as an adapter protein) in invasion might be to ampify signals that lead to cell invasion.

L. Trusolino, A. Bertotti, P. M. Comoglio, A signaling adapter function for α6β4 integrin in the control of HGF-dependent invasive growth. Cell 107, 643-654 (2001). [Online Journal]

Citation: α6β4 Integrin Leads the Invasion. Sci. STKE 2001, tw452 (2001).


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