| First Author | Sarkar S | Year | 2017 |
| Journal | Genes Dev | Volume | 31 |
| Issue | 11 | Pages | 1109-1121 |
| PubMed ID | 28698296 | Mgi Jnum | J:243895 |
| Mgi Id | MGI:5912674 | Doi | 10.1101/gad.296640.117 |
| Citation | Sarkar S, et al. (2017) PRKCI promotes immune suppression in ovarian cancer. Genes Dev 31(11):1109-1121 |
| abstractText | A key feature of high-grade serous ovarian carcinoma (HGSOC) is frequent amplification of the 3q26 locus harboring PRKC-iota (PRKCI). Here, we show that PRKCI is also expressed in early fallopian tube lesions, called serous tubal intraepithelial carcinoma. Transgenic mouse studies establish PRKCI as an ovarian cancer-specific oncogene. Mechanistically, we show that the oncogenic activity of PRKCI relates in part to the up-regulation of TNFalpha to promote an immune-suppressive tumor microenvironment characterized by an abundance of myeloid-derived suppressor cells and inhibition of cytotoxic T-cell infiltration. Furthermore, system-level and functional analyses identify YAP1 as a downstream effector in tumor progression. In human ovarian cancers, high PRKCI expression also correlates with high expression of TNFalpha and YAP1 and low infiltration of cytotoxic T cells. The PRKCI-YAP1 regulation of the tumor immunity provides a therapeutic strategy for highly lethal ovarian cancer. |
