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 M Dong, Kun Ling

Research output: Contribution to journalArticle

7 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)42414-42427
Number of pages14
JournalOncotarget
Volume8
Issue number26
DOIs
StatePublished - 2017

Fingerprint

Phosphatidylinositol Phosphates
Phosphotransferases
Ligands
Triple Negative Breast Neoplasms
Neoplasms
Cell Survival
Up-Regulation
T-Lymphocytes
1-phosphatidylinositol-4-phosphate 5-kinase

Keywords

  • AKT
  • NF-κB
  • PD-L1
  • PIPKIγ
  • Triple negative breast cancer

ASJC Scopus subject areas

  • Oncology

Cite this

Type Iγ phosphatidylinositol phosphate kinase regulates PD-L1 expression by activating NF-κB. / Xue, Junli; Chen, Chunhua; Qi, Manlong; Huang, Yan; Wang, Lin; Gao, Yong; Dong, Haidong M; Ling, Kun.

In: Oncotarget, Vol. 8, No. 26, 2017, p. 42414-42427.

Research output: Contribution to journalArticle

Xue, Junli ; Chen, Chunhua ; Qi, Manlong ; Huang, Yan ; Wang, Lin ; Gao, Yong ; Dong, Haidong M ; Ling, Kun. / Type Iγ phosphatidylinositol phosphate kinase regulates PD-L1 expression by activating NF-κB. In: Oncotarget. 2017 ; Vol. 8, No. 26. pp. 42414-42427.
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