Mutational activation of the phosphatidylinositol 3-kinase (PI3K) pathway occurs in a wide variety of tumors, whereas activating Wnt pathway mutants are predominantly found in colon cancer. Because GSK3 is a key component of both pathways, it is widely assumed that active PI3K signaling feeds positively into the Wnt pathway by protein kinase B (PKB)-mediatefd inhibition of GSK3. In addition, PKB has been proposed to modulate the canonical Wnt signaling through direct stabilization and nuclear localization of beta-catenin. Here, we show that compartmentalization by Axin of GSK3 prohibits cross-talk between the PI3K and Wnt pathways and that Wnt-mediated transcriptional activity is not modulated by activation of the PI3K/PKB pathway.
Ng, S. S., Mahmoudi, T., Danenberg, E. M., Bejaoui, I., de Lau, W. B. M., Korswagen, H. C., Schutte, M., & Clevers, H. (2009). Phosphatidylinositol 3-kinase (PI3K) signaling does not activate the Wnt cascade. Journal of Biological Chemistry, 284(51), 35308-35313. https://doi.org/10.1074/jbc.M109.078261