IGF2BP2 promotes the progression of colorectal cancer through a YAP-dependent mechanism

Cancer Sci. 2021 Oct;112(10):4087-4099. doi: 10.1111/cas.15083. Epub 2021 Aug 3.

Abstract

To explore the effect of insulin-like growth factor 2 mRNA-binding protein 2 (IGF2BP2) on colorectal cancer (CRC) by recognizing the m6A modification of YAP mRNA thus activating ErbB2 expression. High expressions of IGF2BP2, YAP, and ErbB2 promoted the proliferation, migration and invasion of CRC cells and reduced their apoptosis. IGF2BP2 recognized the m6A on YAP mRNA and promoted the translation of mRNA. YAP regulated ErbB2 expression by promoting TEAD4 enrichment in ErbB2 promoter region. Therefore, IGF2BP2 promoted the expression of ErbB2 to enhance the proliferation, invasion and migration of CRC cells, to repress cell apoptosis, and to promote solid tumor formation in nude mice. IGF2BP2 activates the expression of ErbB2 by recognizing the m6A of YAP, thus affecting the cell cycle of CRC, inhibiting cell apoptosis, and promoting proliferation.

Keywords: ErbB2; IGF2BP2; YAP; apoptosis; colorectal cancer; invasion; m6A; migration; proliferation.

MeSH terms

  • Adaptor Proteins, Signal Transducing / metabolism*
  • Animals
  • Apoptosis
  • Cell Cycle
  • Cell Movement
  • Cell Proliferation
  • Colorectal Neoplasms / metabolism*
  • Colorectal Neoplasms / pathology
  • DNA-Binding Proteins / metabolism
  • Disease Progression
  • Humans
  • Methyltransferases / genetics
  • Methyltransferases / metabolism
  • Mice
  • Mice, Nude
  • Muscle Proteins / metabolism
  • Neoplasm Invasiveness
  • Promoter Regions, Genetic
  • Protein Modification, Translational
  • RNA, Messenger / metabolism
  • RNA-Binding Proteins / physiology*
  • Receptor, ErbB-2 / metabolism*
  • TEA Domain Transcription Factors
  • Transcription Factors / metabolism*
  • YAP-Signaling Proteins

Substances

  • Adaptor Proteins, Signal Transducing
  • DNA-Binding Proteins
  • IGF2BP2 protein, human
  • Muscle Proteins
  • RNA, Messenger
  • RNA-Binding Proteins
  • TEA Domain Transcription Factors
  • TEAD4 protein, human
  • Transcription Factors
  • YAP-Signaling Proteins
  • YAP1 protein, human
  • Methyltransferases
  • METTL3 protein, human
  • ERBB2 protein, human
  • Receptor, ErbB-2