ONCOGENESIS Dodging Death, Creating Cancer with Wnt

Teasing apart the actions of oncogenes, which often stimulate apoptotic signaling along with growth-promoting signals, has proven a challenging puzzle, particularly when interactions with other signaling pathways are also integrated into the biological response. You et al. describe experiments that help clarify the interaction of the c-Myc oncogene product with the Wnt--β-catenin signaling. Because Wnt signaling is enhanced in various human cancers and often correlates with increased expression of c-Myc, it might seem that Myc provides a growth-stimulatory effect to cooperate with Wnt signals. However, the data by You et al. suggest that a critical aspect of the interaction is actually for Wnt signals to inhibit Myc's effects that induce apoptosis. Furthermore, Wnt-1 and cMyc cooperated to promote tumor formation when cells expressing both proteins were injected in nude mice. Cyclooxygenase 2 and WISP-1 [Wnt-1 induced secreted protein 1, a member of the CCN (connective tissue growth factor-Cyr61-NOV) family of growth factors] were identified as potential mediators of the effect of Wnt to blunt apoptotic signals. The authors suggest that increased expression of Wnt and c-Myc in cancer cells may allow the cells to tolerate the apoptotic effects of Myc, thus favoring oncogenic transformation.

Z. You, D. Saims, S. Chen, Z. Zhang, D. C. Guttridge, K. Guan, O. A. MacDougald, A. M.C. Brown, G. Evan, J. Kitajewski, C. -Y. Wang, Wnt signaling promotes oncogenic transformation by inhibiting c-Myc-induced apoptosis. J. Cell Biol. 157, 429-440 (2002) [Abstract] [Full Text]