PMID- 33615510
OWN - NLM
STAT- MEDLINE
DCOM- 20210707
LR  - 20231213
IS  - 1099-0844 (Electronic)
IS  - 0263-6484 (Linking)
VI  - 39
IP  - 3
DP  - 2021 Apr
TI  - PTPN6 promotes chemosensitivity of colorectal cancer cells via inhibiting the 
      SP1/MAPK signalling pathway.
PG  - 392-400
LID - 10.1002/cbf.3604 [doi]
AB  - The abnormal expression of protein tyrosine phosphatase nonreceptor type 6 
      (PTPN6) has been proved to be associated with the progression of colorectal 
      cancer. However, its role in chemosensitivity and related molecular mechanism 
      have not been clarified. It has been reported that PTPN6 was down-regulated in 
      colorectal cancer cells compared with the normal colorectal cells. To evaluate 
      the effects of PTPN6 on the proliferation and survival of colorectal cancer 
      cells, PTPN6 was overexpressed in colorectal cancer cells in the present study. 
      We found that cell proliferation and viability were both decreased after 
      overexpression of PTPN6. The IC50 of 5-Fu against colorectal cells was also 
      declined in PTPN6 transfected cells. And further, we verified that PTPN6 could 
      down-regulate the expression of P-gp and MRP-1. Moreover, SP1 was the target 
      protein of PTPN6 predicated by ChIPBase software and confirmed through 
      Co-immunoprecipitation assay and it was negatively regulated by PTPN6. To further 
      verify the effect of SP1 on chemoresistance, SP1 was overexpressed. SP1 
      overexpression enhanced the drug-resistance to 5-Fu and abrogated the effects of 
      PTPN6 upregulation on 5-Fu resistance. All the above changes were associated with 
      the down-regulation of proteins related to MAPK signalling pathway, such as 
      phosphorylation of extracellular regulated protein kinases (ERK) and p38. In 
      summary, PTPN6 promoted chemosensitivity of colorectal cancer cells by targeting 
      SP1 and inhibiting the activation of MAPK signalling pathway. SIGNIFICANCE OF THE 
      STUDY: It has been demonstrated that the abnormal expression of PTPN6 was related 
      to the progression of colorectal cancer. However, the chemosensitivity of PTPN6 
      and its molecular mechanisms were still unclear. Here, we identified that PTPN6 
      was down-regulated in colorectal cancer cells. Moreover, PTPN6 overexpression not 
      only reduced cell proliferation and viability, but decreased the resistance of 
      colorectal cells to 5-Fu. In our research, we found that the SP1 was the target 
      protein of PTPN6 and it was negatively regulated by PTPN6. In addition, SP1 could 
      increase the resistance of colorectal cells to 5-Fu. Molecular mechanism studies 
      have shown that PTPN6 promoted the chemosensitivity of colorectal cancer cells by 
      inhibiting the activation of MAPK signalling pathway.
CI  - (c) 2020 John Wiley & Sons Ltd.
FAU - Fang, Huilong
AU  - Fang H
AD  - Department of Pathogenic Biology and Immunology, Xiangnan University, Chenzhou, 
      China.
FAU - Ma, Wei
AU  - Ma W
AD  - Department of Translational Medicine Collaorative Innovation Center, Shenzhen 
      People's Hospital, Shenzhen, Guangdong, China.
FAU - Guo, Xuli
AU  - Guo X
AD  - Department of Pathogenic Biology and Immunology, Xiangnan University, Chenzhou, 
      China.
FAU - Wang, Junjie
AU  - Wang J
AUID- ORCID: 0000-0003-4979-1934
AD  - Department of Pharmacology, Xiangnan University, Chenzhou, China.
LA  - eng
GR  - 18A458/The Scientific Research Fund of Hunan Provincial Education Department/
PT  - Journal Article
DEP - 20201207
PL  - England
TA  - Cell Biochem Funct
JT  - Cell biochemistry and function
JID - 8305874
RN  - 0 (Neoplasm Proteins)
RN  - 0 (Sp1 Transcription Factor)
RN  - 0 (SP1 protein, human)
RN  - EC 3.1.3.48 (PTPN6 protein, human)
RN  - EC 3.1.3.48 (Protein Tyrosine Phosphatase, Non-Receptor Type 6)
RN  - U3P01618RT (Fluorouracil)
SB  - IM
MH  - Caco-2 Cells
MH  - Colorectal Neoplasms/drug therapy/*metabolism
MH  - Drug Resistance, Neoplasm/*drug effects
MH  - Fluorouracil/*pharmacology
MH  - HCT116 Cells
MH  - HT29 Cells
MH  - Humans
MH  - MAP Kinase Signaling System/*drug effects
MH  - Neoplasm Proteins/*metabolism
MH  - Protein Tyrosine Phosphatase, Non-Receptor Type 6/*metabolism
MH  - Sp1 Transcription Factor/*metabolism
OTO - NOTNLM
OT  - MAPK signalling pathway
OT  - PTPN6
OT  - SP1
OT  - chemosensitivity
OT  - colorectal cancer
EDAT- 2021/02/23 06:00
MHDA- 2021/07/08 06:00
CRDT- 2021/02/22 06:10
PHST- 2020/10/17 00:00 [revised]
PHST- 2020/02/28 00:00 [received]
PHST- 2020/10/24 00:00 [accepted]
PHST- 2021/02/23 06:00 [pubmed]
PHST- 2021/07/08 06:00 [medline]
PHST- 2021/02/22 06:10 [entrez]
AID - 10.1002/cbf.3604 [doi]
PST - ppublish
SO  - Cell Biochem Funct. 2021 Apr;39(3):392-400. doi: 10.1002/cbf.3604. Epub 2020 Dec 
      7.