CCN6: a novel method of aTAKing cancer.

It is well-established that the expression of CCN family of matricellular proteins is altered in essentially all cancers and, hence, targeting these proteins may be a novel therapeutic approach to treating these diseases. For example, CCN6 (WISP3) is downregulated in aggressive breast cancers, and this phenomenon appears to result in the tumor survival by promoting Akt phosphorylation. In a recent report by Pal et al. (Cancer Res 72(18):4818-4828, 2012), CCN6 knockdown was shown to promote BMP4-mediated activation of the Smad-independent TAK1 and p38 kinases. CCN6 expression was inversely associated with BMP4 and phospho-p38 levels in 69 % of invasive breast carcinomas. TAK1 inhibition has been previously shown to decrease tumor progression in preclinical models of TAK1-dependent cancers. These data are consistent with the idea that CCN6 may represent a novel therapeutic approach, as compared to attacking TAK1 directly, to selectively target breast cancers.