- Title
- The ανβ6 integrin regulates its own expression with cell crowding: implications for tumour progression
- Creator
- Niu, J.; Gu, X.; Ahmed, N.; Andrews, S.; Turton, J.; Bates, R.; Agrez, M.
- Relation
- International Journal of Cancer Vol. 92 , Issue 1, p. 40-48
- Publisher Link
- http://dx.doi.org/10.1002/1097-0215(200102)9999:9999<::AID-IJC1157>3.0.CO;2-B
- Publisher
- Wiley-Liss
- Resource Type
- journal article
- Date
- 2001
- Description
- Expression of the growth-promoting integrin ανβ6 in colon cancer cells induces gelatinase B secretion and activation, the inhibition of which abolishes ανβ6-mediated tumour cell growth within a collagen matrix. Herein, we show that high cell density selectively enhances ανβ6 expression in a protein kinase C (PKC)-dependent manner in preference to other 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 ανβ6-expressing cells than for colon cancer cells which lack ανβ6. We propose a self-perpetuating system of colon cancer progression in which the integrin ανβ6 provides a means of sustaining tumour cell proliferation. In this model, ανβ6 regulates its own expression via a PKC-mediated signalling pathway as tumour cells become crowded and quiescent. The ανβ6-mediated induction of gelatinase B secretion facilitates peri-cellular matrix degradation, which helps overcome crowding and restores cell proliferation.
- Subject
- ανβ6; integrins; cell density; colon cancer; gelatinase B
- Identifier
- uon:1087
- Identifier
- http://hdl.handle.net/1959.13/26745
- Identifier
- ISSN:0020-7136
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