@article{1508e19794074be68eb490384f6abd1b,
title = "Type Iγ phosphatidylinositol phosphate kinase regulates PD-L1 expression by activating NF-κB",
abstract = "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.",
keywords = "AKT, NF-κB, PD-L1, PIPKIγ, Triple negative breast cancer",
author = "Junli Xue and Chunhua Chen and Manlong Qi and Yan Huang and Lin Wang and Yong Gao and Haidong Dong and Kun Ling",
note = "Funding Information: We would like to thank Drs. Haojie Huang, Yanan Yang and Jinghua Hu at Mayo Clinic for kindly sharing reagents and equipment, Dr. Qingwen Xu for discussion, and Drs. Yan Li, Yingyi Zhang and Xin Liu for technical support. This work was supported by the grant 81502510 from the Natural Science Foundation of China to J.X., the Key Disciplines Group Construction Project of Pudong Health Bureau of Shanghai (PWZxq2014-04), a grant 201440318 from Shanghai Municipal Commission of Health and Family Planning, a grant DFZY-12 from Shanghai East Rising Sun Program; Shanghai Youth Doctor Training Program, Mayo Clinic Breast Cancer SPORE development award to H.D., Mayo Clinic Center of Biomedical Discovery Team Science Platform Award to H.D. and K.L., and R01CA149039 from National Cancer Institute, United States of the America to K.L. Publisher Copyright: {\textcopyright} Junli Xue et al. Copyright: Copyright 2017 Elsevier B.V., All rights reserved.",
year = "2017",
doi = "10.18632/oncotarget.17123",
language = "English (US)",
volume = "8",
pages = "42414--42427",
journal = "Oncotarget",
issn = "1949-2553",
publisher = "Impact Journals",
number = "26",
}