Figure 1. WNT signaling in cancer. A Boston-based team and a Genentech Inc.-led team have each identified a new kinase-v-yes-1 Yamaguchi sarcoma viral oncogene homolog 1 (YES1; Yes) and receptor-interacting serine-threonine
kinase 4
(RIPK4; RIP4), respectively-that acts in wingless-type MMTV integration site (WNT)-driven cancers.

The Genentech team found that RIPK4 acts at the WNT receptor complex to phosphorylate dishevelled dsh homolog 2 (DVL2). This induces b-catenin (CTNNB1) accumulation in the cytoplasm (I[a]) and translocation to the nucleus to regulate gene expression via the TCF family of transcription factors (I[b]).
RIPK4 also appears to play a role in cancer cells (II[a]), as the kinase is overexpressed in ovarian cancers, and knocking down RIPK4 in a cancer cell line decreased tumor growth in mice.

The Boston team found that in cancer cell lines with increased b-catenin activity, b-catenin forms a transcriptional complex with yes-associated protein 1 (YAP1) and YES1 that regulates the increased expression of antiapoptotic genes (II[b]). Knocking down YES1 decreased the formation of WNT-driven colon tumors in mice.