Nonreceptor tyrosine phosphatase 14 promotes proliferation and migration through regulating phosphorylation of YAP of Hippo signaling pathway in gastric cancer cells

J Cell Biochem. 2019 Oct;120(10):17723-17730. doi: 10.1002/jcb.29038. Epub 2019 Jun 6.

Abstract

Background: The Hippo signaling pathway is associated with cell proliferation and organ size, and its transcriptional coactivator Yes-associated protein (YAP), emerges as a crucial oncoprotein in multiple cancers. It was increasingly recognized that nonreceptor tyrosine phosphatase 14 (PTPN14) was relevant to the cell membrane and cytoskeleton, and had a critical effect on cell adhesion, growth, and actin cytoskeleton organization. Furthermore, PTPN14 was also certified to operate the translocation and phosphorylation of YAP. The present experiment was aimed to explore the impact of PTPN14 on gastric cancer (GC) cell proliferation and migration through regulating the phosphorylation of YAP.

Methods: The pEGFP-N1-PTPN14 recombinant plasmid was stably transfected into three differentiation degrees GC cell lines, including MKN-28, SGC-7901, and BGC-823. Quantitative reverse transcription-polymerase chain reaction and Western blot assay were performed to analyze the messenger RNA (mRNA) and protein levels. The proliferative and migratory capacity of cells was appraised by Cell Counting Kit-8 assay and transwell chamber.

Results: Compared with the normal control and vector transfection group, the capacity of these three cell lines, which transfected with the pEGFP-N1-PTPN14 to proliferate and migrate in vitro was increased obviously (P < .05). There was no YAP mRNA detected in MKN-28 cell line. Meanwhile, after transfecting the pEGFP-N1-PTPN14 plasmid, the mRNA level of YAP in SGC-7901 was reduced (P < .05), and it was increased in BGC-823 (P < .05). The YAP protein level in SGC-7901 and BGC-823 has no apparent transformation by transfecting, but the protein level of phospho-Ser127 YAP and phospho-Ser397 YAP is upregulated (P < .05).

Conclusion: PTPN14 could enhance the proliferative and migratory ability of GC cells by promoting the YAP phosphorylation in the Hippo signaling pathway. Taken together, PTPN14 might be involved in the occurrence and development of GC and become a molecular regulator to treat GC.

Keywords: Hippo signaling pathway; PTPN14; YAP; gastric cancer; phosphorylated YAP.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing / metabolism*
  • Cell Line, Tumor
  • Cell Movement* / genetics
  • Cell Proliferation
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Phosphorylation
  • Protein Tyrosine Phosphatases, Non-Receptor / genetics
  • Protein Tyrosine Phosphatases, Non-Receptor / metabolism*
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Signal Transduction*
  • Stomach Neoplasms / genetics
  • Stomach Neoplasms / pathology*
  • Transcription Factors / metabolism*
  • YAP-Signaling Proteins

Substances

  • Adaptor Proteins, Signal Transducing
  • RNA, Messenger
  • Transcription Factors
  • YAP-Signaling Proteins
  • YAP1 protein, human
  • PTPN14 protein, human
  • Protein Tyrosine Phosphatases, Non-Receptor