First published online March 10, 2005
Journal of Cell Science 118, 603e (2005)
© The Company of Biologists Limited
Integrins look to mRNA to remodel
Remodelling of the extracellular matrix (ECM) by matrix metalloproteinases (MMPs) is important for development, would healing and tumorigenesis. Expression of MMPs is regulated by extracellular stimuli such as growth factors and cytokines. Integrins – which physically link cells to the ECM – can also regulate MMPs, but how they do so is unclear. On p. 1185, Michael DiPersio and co-workers show that 
3ß1, an integrin implicated in tumour progression, acts at the mRNA level. They have examined induction of MMP-9 by the Ras oncogene in 3-null and wild-type keratinocytes. The authors demonstrate that 3 is required for stimulation of MMP-9 synthesis by the Ras/ERK MAP kinase pathway. Interestingly, they find that Ras-mediated activation of ERK and ERK-dependent activation of the MMP-9 promoter are both unaffected by loss of 3. The stability of MMP-9 mRNA, however, is significantly reduced in the 3-null cells. DiPersio and co-workers therefore conclude that signalling by 3ß1 stabilizes MMP-9 mRNA. Such post-transcriptional regulation adds an interesting twist to the well-established cooperation between integrin and MAP kinase signalling and could be important during malignant progression of squamous cell carcinoma and other tissue-remodelling events in which 3ß1 is implicated.
Related articles in JCS:
- 3ß1 integrin regulates MMP-9 mRNA stability in immortalized keratinocytes: a novel mechanism of integrin-mediated MMP gene expression
- Vandana Iyer, Kevin Pumiglia, and C. Michael DiPersio
JCS 2005 118: 1185-1195.
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