| First Author | Hsu AH | Year | 2018 |
| Journal | Cell Rep | Volume | 24 |
| Issue | 3 | Pages | 655-669 |
| PubMed ID | 30021163 | Mgi Jnum | J:271298 |
| Mgi Id | MGI:6278562 | Doi | 10.1016/j.celrep.2018.06.067 |
| Citation | Hsu AH, et al. (2018) Crosstalk between PKCalpha and PI3K/AKT Signaling Is Tumor Suppressive in the Endometrium. Cell Rep 24(3):655-669 |
| abstractText | Protein kinase C (PKC) isozymes are commonly recognized as oncoproteins based on their activation by tumor-promoting phorbol esters. However, accumulating evidence indicates that PKCs can be inhibitory in some cancers, with recent findings propelling a shift in focus to understanding tumor suppressive functions of these enzymes. Here, we report that PKCalpha acts as a tumor suppressor in PI3K/AKT-driven endometrial cancer. Transcriptional suppression of PKCalpha is observed in human endometrial tumors in association with aggressive disease and poor prognosis. In murine models, loss of PKCalpha is rate limiting for endometrial tumor initiation. PKCalpha tumor suppression involves PP2A-family-dependent inactivation of AKT, which can occur even in the context of genetic hyperactivation of PI3K/AKT signaling by coincident mutations in PTEN, PIK3CA, and/or PIK3R1. Together, our data point to PKCalpha as a crucial tumor suppressor in the endometrium, with deregulation of a PKCalpha-->PP2A/PP2A-like phosphatase signaling axis contributing to robust AKT activation and enhanced endometrial tumorigenesis. |
