Volume 30, No 7, Jul 2020

ISSN: 1001-0602 
EISSN: 1748-7838 2018 
impact factor 17.848* 
(Clarivate Analytics, 2019)

Volume 30 Issue 7, July 2020: 590-601   |  Open Access

ORIGINAL ARTICLES

Regulation of sister chromatid cohesion by nuclear PD-L1

Jia Yu^1,† , Bo Qin^1,2,† , Ann M. Moyer^3,4 , Xinyi Tu² , Haidong Dong⁵ , Judy C. Boughey⁶ , Matthew P. Goetz^1,2 , Richard Weinshilboum¹ , Zhenkun Lou^2,* , Liewei Wang^1,*

¹Department of Molecular Pharmacology and Experimental Therapeutics, Mayo Clinic, Rochester, MN 55905, USA;
²Department of Oncology, Mayo Clinic, Rochester, MN 55905, USA;
³Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN 55905, USA;
⁴Mayo Clinic Graduate School of Biomedical Sciences, Mayo Clinic School of Medicine and the Mayo Clinic Medical Scientist Training Program, Mayo Clinic, Rochester, MN 55905, USA;
⁵Departments of Urology and Immunology, Mayo Clinic, Rochester, MN 55905, USA;
⁶Department of Surgery, Mayo Clinic, Rochester, MN 55905, USA
^†These authors contributed equally
Correspondence: Zhenkun Lou(Lou.Zhenkun@mayo.edu)Liewei Wang(Wang.Liewei@mayo.edu)

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.

https://doi.org/10.1038/s41422-020-0315-8

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