Type Iγ phosphatidylinositol phosphate kinase regulates PD-L1 expression by activating NF-κB
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Junli Xue1,2, Chunhua Chen2, Manlong Qi2,3, Yan Huang2, Lin Wang2,4, Yong Gao1, Haidong Dong5 and Kun Ling2
1Department of Oncology, Shanghai East Hospital, Tongji University School of Medicine, Shanghai 200120, China
2Department of Biochemistry and Molecular Biology, Mayo Clinic, Rochester, MN 55902, USA
3Department of Clinical Genetics, Shengjing Hospital of China Medical University, Shenyang 110004, Liaoning Province, China
4Department of Oncology, Guangzhou Red Cross Hospital, Guangzhou 510220, Guangdong Province, China
5Department of Urology, Mayo Clinic, Rochester, MN 55902, USA
Kun Ling, email: firstname.lastname@example.org
Yong Gao, email: email@example.com
Keywords: PD-L1, triple negative breast cancer, PIPKIγ, NF-κB, AKT
Received: December 16, 2016 Accepted: April 01, 2017 Published: April 15, 2017
The programmed death-ligand 1 (PD-L1), by binding to PD-1 on the surface of immune cells, activates a major immune checkpoint pathway. Elevated expression of PD-L1 in tumor cells mediates tumor-induced T-cell exhaustion and immune suppression; therefore protect the survival of tumor cells. Although blockade of the PD-1/PD-L1 axis exhibits great potential in cancer treatment, mechanisms driving the up-regulation of PD-L1 in tumor cells remain not fully understood. Here we found that type Iγ phosphatidylinositol 4-phosphate (PtdIns(4)P) 5-kinase (PIPKIγ) is required for PD-L1 expression in triple negative breast cancer cells. Depletion of PIPKIγ inhibits both intrinsic and induced PD-L1 expression. Results from further analyses suggest that PIPKIγ promotes the transcription of the PD-L1 gene by activating the NF-κB pathway in these cells. These results demonstrate that PIPKIγ-dependent expression of PD-L1 is likely important for the progression of triple negative breast cancer.
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