Myc (arrow, top), but not Myc plus Wnt-1 (bottom) induces apoptosis in tumors.

To be successful, a tumorigenic cell must not only multiply but also fail to die. You et al. report that Wnt-1 contributes to both sides of this equation. Wnt-1 cooperates with Myc in promoting cell division, and blocks Myc's propensity to cause apoptotic cell death (page 429).

As a tumor promoter, Myc's apoptosis-promoting properties were paradoxical. Now, You et al. find that autocrine or paracrine coexpression of Wnt-1 with Myc prevents this apoptosis. Two Wnt-1 targets—WISP-1 and the cyclooxygenase Cox2—were induced in these cells. They can act together, and independently of Wnt-1, to reduce apoptosis sharply.Cells expressing Myc alone formed small tumors with many apoptotic cells, whereas cells coexpressing Myc and Wnt-1 formed large tumors. This may explain the coincidence of mutations in the Myc and Wnt pathways in many human tumors. Early loss of control over the Wnt pathway may both promote cell growth and inhibit apoptosis, with later mutations in proteins such as Myc accelerating the growth process. ▪