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Molecular Biology of the Cell logoLink to Molecular Biology of the Cell
. 1995 Jun;6(6):725–740. doi: 10.1091/mbc.6.6.725

Integrin alpha 5 beta 1 expression negatively regulates cell growth: reversal by attachment to fibronectin.

J A Varner 1, D A Emerson 1, R L Juliano 1
PMCID: PMC301232  PMID: 7579691

Abstract

Cells selected for overexpression of the integrin alpha 5 beta 1 show decreased proliferation and loss of the transformed phenotype. We provide evidence that de novo expression of the integrin alpha 5 beta 1 in HT29 colon carcinoma cells results in the growth arrest of these cells as characterized by reduced DNA synthesis and cellular proliferation in vitro. In fact, expression of integrin alpha 5 beta 1 on these cells induces the transcription of growth arrest specific gene 1 (gas-1), a gene product known to induce cellular quiescence, but blocks transcription of the immediate early genes c-fos, c-jun, and jun B. In vivo, the alpha 5 beta 1 transfectants display dramatically reduced tumorigenicity as well as a highly differentiated phenotype when compared with their pSVneo-transfected counterparts. Surprisingly, ligation of alpha 5 beta 1 on these cells by cell attachment to a fibronectin substrate not only reverses the growth inhibition and gas-1 gene induction but activates immediate early gene transcription. These findings demonstrate that integrin alpha 5 beta 1 expression in the absence of attachment to fibronectin activates a signaling pathway leading to decreased cellular proliferation and that ligation of this receptor with fibronectin reverses this signal, thereby contributing to the proliferation of transformed cells.

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