PMID- 28881828
OWN - NLM
STAT- PubMed-not-MEDLINE
DCOM- 20170925
LR  - 20181113
IS  - 1949-2553 (Electronic)
IS  - 1949-2553 (Linking)
VI  - 8
IP  - 32
DP  - 2017 Aug 8
TI  - SHP2 negatively regulates HLA-ABC and PD-L1 expression via STAT1 phosphorylation 
      in prostate cancer cells.
PG  - 53518-53530
LID - 10.18632/oncotarget.18591 [doi]
AB  - 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.
FAU - Liu, Zhuqing
AU  - Liu Z
AD  - Department of Medical Oncology, Shanghai Tenth People's Hospital, Tongji 
      University, School of Medicine, Shanghai 200072, China.
FAU - Zhao, Yu
AU  - Zhao Y
AD  - Department of Medical Oncology, Shanghai Tenth People's Hospital, Tongji 
      University, School of Medicine, Shanghai 200072, China.
FAU - Fang, Juemin
AU  - Fang J
AD  - Department of Medical Oncology, Shanghai Tenth People's Hospital, Tongji 
      University, School of Medicine, Shanghai 200072, China.
FAU - Cui, Ran
AU  - Cui R
AD  - Department of Medical Oncology, Shanghai Tenth People's Hospital, Tongji 
      University, School of Medicine, Shanghai 200072, China.
FAU - Xiao, Yuanyuan
AU  - Xiao Y
AD  - Department of Medical Oncology, Shanghai Tenth People's Hospital, Tongji 
      University, School of Medicine, Shanghai 200072, China.
FAU - Xu, Qing
AU  - Xu Q
AD  - Department of Medical Oncology, Shanghai Tenth People's Hospital, Tongji 
      University, School of Medicine, Shanghai 200072, China.
LA  - eng
PT  - Journal Article
DEP - 20170621
PL  - United States
TA  - Oncotarget
JT  - Oncotarget
JID - 101532965
PMC - PMC5581127
OTO - NOTNLM
OT  - HLA-ABC
OT  - PD-L1
OT  - SHP2
OT  - STAT1
OT  - prostate cancer
COIS- CONFLICTS OF INTEREST The authors declare that they have no competing financial 
      interests.
EDAT- 2017/09/09 06:00
MHDA- 2017/09/09 06:01
PMCR- 2017/08/08
CRDT- 2017/09/09 06:00
PHST- 2016/12/14 00:00 [received]
PHST- 2017/05/22 00:00 [accepted]
PHST- 2017/09/09 06:00 [entrez]
PHST- 2017/09/09 06:00 [pubmed]
PHST- 2017/09/09 06:01 [medline]
PHST- 2017/08/08 00:00 [pmc-release]
AID - 18591 [pii]
AID - 10.18632/oncotarget.18591 [doi]
PST - epublish
SO  - Oncotarget. 2017 Jun 21;8(32):53518-53530. doi: 10.18632/oncotarget.18591. 
      eCollection 2017 Aug 8.