Research Papers:

Type Iγ phosphatidylinositol phosphate kinase regulates PD-L1 expression by activating NF-κB

Junli Xue, Chunhua Chen, Manlong Qi, Yan Huang, Lin Wang, Yong Gao, Haidong Dong and Kun Ling _

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Oncotarget. 2017; 8:42414-42427. https://doi.org/10.18632/oncotarget.17123

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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

Correspondence to:

Kun Ling, email: [email protected]

Yong Gao, email: [email protected]

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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