The Proto-oncogene Bcl3 Induces Immune Checkpoint PD-L1 Expression, Mediating Proliferation of Ovarian Cancer Cells

Overview

Journal J Biol Chem

Specialty Biochemistry

Date 2018 Aug 24

PMID 30135206

Citations 30

Authors

Yue Zou

Mohammad M Uddin

Sveta Padmanabhan

Yan Zhu

Pengli Bu

Ales Vancura

Ivana Vancurova

Affiliations

Soon will be listed here.

Abstract

The proto-oncogene Bcl3 induces survival and proliferation in cancer cells; however, its function and regulation in ovarian cancer (OC) remain unknown. Here, we show that expression is increased in human OC tissues. Surprisingly, however, we found that in addition to promoting survival, proliferation, and migration of OC cells, Bcl3 promotes both constitutive and interferon-γ (IFN)-induced expression of the immune checkpoint molecule PD-L1. The Bcl3 expression in OC cells is further increased by IFN, resulting in increased transcription. The mechanism consists of an IFN-induced, Bcl3- and p300-dependent promoter occupancy by Lys-314/315 acetylated p65 NF-κB. Blocking PD-L1 by neutralizing antibody reduces proliferation of OC cells overexpressing Bcl3, suggesting that the pro-proliferative effect of Bcl3 in OC cells is partly mediated by PD-L1. Together, this work identifies PD-L1 as a novel target of Bcl3, and links Bcl3 to IFNγ signaling and PD-L1-mediated immune escape.

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