Integrins make a choice
نویسنده
چکیده
Integrins make a choice ignaling researchers have only a few factors with which to explain a whole lot of biology. On page 407, Goel et al. describe how two integrin variants channel the actions of a single factor, insulin-like growth factor (IGF), into two distinct pathways that induce either adhesion or proliferation. The  1A integrin variant was known to be associated with proliferation and the  1C variant to inhibit it. IGF and its receptors had also been found to enhance adhesion through  1 integrins. Goel et al. find that, in cells with  1A integrin, IGF binding to its receptor induces formation of a ternary complex of integrin, IGF receptor and the downstream signaling protein IRS-1. The resultant boost in cell proliferation is, however, prevented by expression of the  1C inte-grin. A short insertion in the cytoplasmic tail of  1C brings in the Gab1 and Shp2 proteins, with the Shp2 phosphatase removing the phosphates that would otherwise have led to IRS-1 recruitment and signaling. The result is synergistic activation of adhesion by the IGF receptor and  1C integrin. It is not yet clear which molecular output the IGF receptor is bringing to the adhesion equation. But removal of  1C with a ribozyme prevents IGF-stimulated adhesion, and  1C addition to prostate tumor cells before their injection into host animals significantly reduces the size of the resultant tumors. S IGF and integrins can collaborate in either adhesion or proliferation. ost cells undergo a form of apoptosis called anoikis when they are grown in suspension. Janes and Watt report on page 419 that squamous cell carcinomas (SCCs) avoid this fate by expressing an alternative integrin called ␣ v  6. The pathway may be appropriated from cells that require a temporary M Addition of an integrin (right) prevents anchorage-independent growth. reprieve from substrate-dependent growth during differentiation or tissue repair. The ␣ v  6 integrin is known to favor tumor formation by increasing cell invasion and proliferation and inhibiting matrix assembly, but the new study is the first to demonstrate its ability to confer a survival advantage. The authors introduced ␣ v into an ␣ v-null cell line and showed that suspended transfectants died because their ␣ v  5 acted via caspase 8 to suppress activation of an Akt survival signal. Addition of both ␣ v and  6 , however, resulted in …
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ورودعنوان ژورنال:
- The Journal of Cell Biology
دوره 166 شماره
صفحات -
تاریخ انتشار 2004