YTH domain family 2 orchestrates epithelial-mesenchymal transition/proliferation dichotomy in pancreatic cancer cells

Cell Cycle. 2017;16(23):2259-2271. doi: 10.1080/15384101.2017.1380125. Epub 2017 Nov 14.

Abstract

Recent studies show that YTH domain family 2 (YTHDF2) preferentially binds to m6A-containing mRNA regulates localization and stability of the bound mRNA. However, the role of YTHDF2 in pancreatic cancers remains to be elucidated. Here, we find that YTHDF2 expression is up-regulated in pancreatic cancer tissues compared with normal tissues at both mRNA and protein levels, and is higher in clinical patients with later stages of pancreatic cancer, indicating that YTHDF2 possesses potential clinical significance for diagnosis and prognosis of pancreatic cancers. Furthermore, we find that YTHDF2 orchestrates two cellular processes: promotes proliferation and inhibits migration and invasion in pancreatic cancer cells, a phenomenon called "migration-proliferation dichotomy", as well as epithelial-mesenchymal transition (EMT) in pancreatic cancer cells. Furthermore, YTHDF2 knockdown significantly increases the total YAP expression, but inhibits TGF-β/Smad signaling, indicating that YTHDF2 regulates EMT probably via YAP signaling. In summary, all these findings suggest that YTHDF2 may be a new predictive biomarker of development of pancreatic cancer, but a serious consideration is needed to treat YTHDF2 as a target for pancreatic cancer.

Keywords: EMT; YAP; YTHDF2; migration-proliferation dichotomy; pancreatic cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing / metabolism
  • Cell Line, Tumor
  • Cell Movement
  • Cell Proliferation*
  • Epithelial-Mesenchymal Transition*
  • G1 Phase Cell Cycle Checkpoints
  • Humans
  • Neoplasm Staging
  • Pancreatic Neoplasms / metabolism
  • Pancreatic Neoplasms / pathology*
  • Phosphoproteins / metabolism
  • Proto-Oncogene Proteins c-akt / metabolism
  • RNA Interference
  • RNA, Small Interfering / metabolism
  • RNA-Binding Proteins / antagonists & inhibitors
  • RNA-Binding Proteins / genetics
  • RNA-Binding Proteins / metabolism*
  • Signal Transduction
  • Smad Proteins / metabolism
  • Transcription Factors
  • Transforming Growth Factor beta / metabolism
  • Up-Regulation

Substances

  • Adaptor Proteins, Signal Transducing
  • Phosphoproteins
  • RNA, Small Interfering
  • RNA-Binding Proteins
  • Smad Proteins
  • Transcription Factors
  • Transforming Growth Factor beta
  • YAP1 (Yes-associated) protein, human
  • YTHDF2 protein, human
  • Proto-Oncogene Proteins c-akt

Grant support

This study was supported by grants from the National Natural Science Foundation of China (81472333, 81372718, 81672402) and the Natural Science Foundation of Jiangsu Province (BK20131247).