PRKCI promotes immune suppression in ovarian cancer

A key feature of high-grade serous ovarian carcinoma (HGSOC) is frequent amplification of the 3q26 locus harboring ( ). Here, we show that PRKCI is also expressed in early fallopian tube lesions, called serous tubal intraepithelial carcinoma. Transgenic mouse studies establish as an ovarian cancer-s...

Ausführliche Beschreibung

Gespeichert in:
Bibliographische Detailangaben
Veröffentlicht in:Genes & development 2017-06, Vol.31 (11), p.1109-1121
Hauptverfasser: Sarkar, Sharmistha, Bristow, Christopher A, Dey, Prasenjit, Rai, Kunal, Perets, Ruth, Ramirez-Cardenas, Alejandra, Malasi, Shruti, Huang-Hobbs, Emmet, Haemmerle, Monika, Wu, Sherry Y, McGuire, Michael, Protopopov, Alexei, Jiang, Shan, Liu, Joyce F, Hirsch, Michelle S, Chang, Qing, Lazar, Alexander J, Sood, Anil K, Drapkin, Ronny, DePinho, Ronald, Draetta, Giulio, Chin, Lynda
Format: Artikel
Sprache:eng
Schlagworte:
Online-Zugang:Volltext
Tags: Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
Beschreibung
Zusammenfassung:A key feature of high-grade serous ovarian carcinoma (HGSOC) is frequent amplification of the 3q26 locus harboring ( ). Here, we show that PRKCI is also expressed in early fallopian tube lesions, called serous tubal intraepithelial carcinoma. Transgenic mouse studies establish as an ovarian cancer-specific oncogene. Mechanistically, we show that the oncogenic activity of PRKCI relates in part to the up-regulation of TNFα 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 TNFα 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.
ISSN:0890-9369
1549-5477
DOI:10.1101/gad.296640.117