Regulation of sister chromatid cohesion by nuclear PD-L1
Open Access
- 29 April 2020
- journal article
- research article
- Published by Springer Science and Business Media LLC in Cell Research
- Vol. 30 (7), 590-601
- https://doi.org/10.1038/s41422-020-0315-8
Abstract
Programmed death ligand-1 (PD-L1 or B7-H1) is well known for its role in immune checkpoint regulation, but its function inside the tumor cells has rarely been explored. Here we report that nuclear PD-L1 is important for cancer cell sister chromatid cohesion. We found that depletion of PD-L1 suppresses cancer cell proliferation, colony formation in vitro, and tumor growth in vivo in immune-deficient NSG mice independent of its role in immune checkpoint. Specifically, PD-L1 functions as a subunit of the cohesin complex, and its deficiency leads to formation of multinucleated cells and causes a defect in sister chromatid cohesion. Mechanistically, PD-L1 compensates for the loss of Sororin, whose expression is suppressed in cancer cells overexpressing PD-L1. PD-L1 competes with Wing Apart-Like (WAPL) for binding to PDS5B, and secures proper sister chromatid cohesion and segregation. Our findings suggest an important role for nuclear PD-L1 in cancer cells independent of its function in immune checkpoint.Keywords
Funding Information
- Foundation for the National Institutes of Health (CA 196648, CA130996, CA203561)
- U.S. Department of Health & Human Services | NIH | National Cancer Institute (P50CA 116201-9)
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