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The αvβ6 integrin regulates its own expression with cell crowding: Implications for tumour progression
Author(s) -
Niu J.,
Gu X.,
Ahmed N.,
Andrews S.,
Turton J.,
Bates R.,
Agrez M.
Publication year - 2001
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/1097-0215(200102)9999:9999<::aid-ijc1157>3.0.co;2-b
Subject(s) - integrin , cell growth , protein kinase c , microbiology and biotechnology , secretion , biology , cancer cell , cancer research , cell , cell culture , cell migration , signal transduction , cancer , endocrinology , biochemistry , genetics
Expression of the growth‐promoting integrin αvβ6 in colon cancer cells induces gelatinase B secretion and activation, the inhibition of which abolishes αvβ6‐mediated tumour cell growth within a collagen matrix. Herein, we show that high cell density selectively enhances αvβ6 expression in a protein kinase C (PKC)–dependent manner in preference to other β integrin subunits, resulting in a marked increase in gelatinase B secretion as cells reach confluence. Moreover, PKC activity increases with cell confluence, and the rise in PKC activity is much greater for αvβ6‐expressing cells than for colon cancer cells which lack αvβ6. We propose a self‐perpetuating system of colon cancer progression in which the integrin αvβ6 provides a means of sustaining tumour cell proliferation. In this model, αvβ6 regulates its own expression via a PKC‐mediated signalling pathway as tumour cells become crowded and quiescent. The αvβ6‐mediated induction of gelatinase B secretion facilitates peri‐cellular matrix degradation, which helps overcome crowding and restores cell proliferation. © 2001 Wiley‐Liss, Inc.