WDR26 in Advanced Breast Cancer: A Novel Regulator of The PI3K/AKT Pathway
Technical Report,30 Sep 2014,29 Sep 2018
University of Iowa Iowa City United States
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The PI3KAKT pathway is one of the most deregulated pathways in breast cancers 70 percent, and a major contributor to tumor progression. PI3Ks and AKTs comprise of multiple isoforms that play a critical role in a wide variety of physiological progresses. Moreover, during cancer progression, different PI3K and AKT isoforms may have different and even opposite roles. Notably, PI3KBeta and AKT2 have been identified as the major isoform that contribute to breast cancer growth and metastasis. Yet, it is not yet clear how to specifically target the PI3KBetaAKT2 without causing wide spread side effects. In this proposal, we aim to test the hypothesis that WDR26 functions as a novel regulator of the PI3KBetaAKT2 pathway, and a previously unidentified markertherapeutic target in advanced breast cancer, in particular, triple negative breast cancer TNBC. Our results demonstrated that WDR26 selectively interacts with GBetagamma, PI3KBeta, and AKT2 and serves as a scaffold that fosters their interaction to promote PI3KAKT activation and in highly malignant and invasive breast tumors, upregulated WDR26 overactivates the PI3KBetaAKT2 pathway, promoting breast tumor growth and metastasis. These findings thus pinpoint WDR26 as a potential therapeutic target for disrupting PI3KAKT overactivation and breast cancer progression.
- Medicine and Medical Research