Editors' ChoiceCell Extravasation

Unraveling Cell Migration and Survival

Science's STKE  11 Apr 2000:
Vol. 2000, Issue 27, pp. tw7
DOI: 10.1126/stke.2000.27.tw7

Cell migration occurs under normal conditions and conditions of cellular dysregulation. Although it is known that the intracellular signals that lead to migration also suppress apoptosis, the molecular components required for both functions are not well characterized. Through the use of three-dimensional collagen matrix cell culture, Cho and Klemke identify several signaling proteins involved in migration and inhibition of apoptosis. COS-7 cells treated with growth factors migrated more and were spared from apoptosis, whereas untreated cells did not migrate and became apoptotic. Anti-integrin antibody treatment of COS-7 cells indicated an essential role for the integrin receptor in cellular migration and apoptosis inhibition. Overexpression of activated MEK, or the Crk-associated substrate (Cas) and Crk together in COS-7 cells greatly increased migration and survival. Similarly, overexpression of Cas and Crk mutants, which cannot associate, greatly diminished the cellular capacity to migrate and survive. The inactivation of ERK by the addition of a MEK inhibitor, in the presence of insulin or EGF but not fetal bovine serum (FBS), resulted in decreased migration and survival, indicating that FBS has components that promote cell migration and survival in an Erk-independent manner. Last, the authors identified that Rac activity is required for Cas/Crk-dependent migration and survival, whereas myosin light chain kinase (MLCK) is required for Erk-dependent functions. Thus, the activation of at least two independent pathways leads to migration and survival in cells.

Cho, S.Y., and Klemke, R.L. (2000) Extracellular-regulated kinase activation and CAS/Crk coupling regulate cell migration and suppress apoptosis during invasion of the extracellular matrix. J. Cell Biol. 149: 223-236. [Abstract] [Full Text]

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