Regulation of sister chromatid cohesion by nuclear PD-L1

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3 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)590-601
Number of pages12
JournalCell Research
Volume30
Issue number7
DOIs
StatePublished - Jul 1 2020

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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