Oncotarget

Research Papers:

SHP2 negatively regulates HLA-ABC and PD-L1 expression via STAT1 phosphorylation in prostate cancer cells

Zhuqing Liu, Yu Zhao, Juemin Fang, Ran Cui, Yuanyuan Xiao and Qing Xu _

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Oncotarget. 2017; 8:53518-53530. https://doi.org/10.18632/oncotarget.18591

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Abstract

Zhuqing Liu1, Yu Zhao1, Juemin Fang1, Ran Cui1, Yuanyuan Xiao1 and Qing Xu1

1Department of Medical Oncology, Shanghai Tenth People’s Hospital, Tongji University, School of Medicine, Shanghai 200072, China

Correspondence to:

Qing Xu, email: qingxumed@163.com

Keywords: prostate cancer, SHP2, STAT1, HLA-ABC, PD-L1

Received: December 14, 2016    Accepted: May 22, 2017    Published: June 21, 2017

ABSTRACT

Src homology region 2-containing protein tyrosine phosphatase 2 (SHP2) is a ubiquitous protein tyrosine phosphatase that activates the signal transduction pathways of several growth factors and cytokines. In our study, SHP2 expression was very high in prostate cancer (PCa) cell lines, and the expression of phospho-signal transducer and activator of transcription 1 (p-STAT1) and STAT1 was very low. SHP2 knockdown upregulated the expression of p-STAT1 and downregulated phospho-extracellular signal regulated kinase (p-ERK). SHP2 depletion also increased the expression of human leukocyte antigen (HLA)-ABC and programmed death ligand 1 (PD-L1). When tumor cells were pretreated with Janus kinase 2 (JAK2) inhibitor, SHP2 depletion failed to induce HLA-ABC and PD-L1 expression. Furthermore, treating tumor cells with the mitogen-activated protein kinase/extracellular signal-regulated kinase (MEK) inhibitor PD0325901 did not upregulate HLA-ABC and PD-L1. SHP2 depletion was associated with increased T-cell activation (CD25 MFI of CD8+) by coculture of allogeneic healthy donor peripheral blood monocytes (PBMC) with SHP2 siRNA pretreated PCa cell lines. These results show that SHP2 targeting upregulates HLA-ABC and PD-L1 expression via STAT1 phosphorylation in PCa cells and SHP2 depletion could increase T-cell activation.


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