S100A4 protects gastric cancer cells from anoikis through regulation of αv and α5 integrin

Detachment from the extracellular matrix induces a form of programmed cell death termed anoikis. Resistance to anoikis permits cancer cells to survive in systemic circulation and facilitates their metastasis to distant organs. It is well known that S100A4 is overexpressed in many tumors and involved in tumor metastasis, but the mechanisms of the metastasis-promoting function of S100A4 are not fully understood. We hypothesized that S100A4 might play a role in anoikis of gastric cancer cells and further affects their metastasis. To test this hypothesis, we changed the expression of S100A4 by means of RNA interference or experimental overexpression and investigated the effect on anoikis. We found that knockdown of S100A4 by RNA interference led to significantly increased anoikis, whereas overexpression of S100A4 resulted in inhibition of anoikis. Furthermore, we provide evidence that inhibition of S100A4 resulted in the downregulation of alpha 5 and alpha v integrin expression. These findings suggest that S100A4 protects gastric cancer cells from anoikis by regulation of alpha v and alpha 5 integrin expression, which sheds a novel light for the role of S100A4 in cancer metastasis. (Cancer Sci 2011; 102: 1014-1018).