Chondroitin polymerizing factor (CHPF) promotes development of malignant melanoma through regulation of CDK1

Cell Death Dis. 2020 Jul 1;11(7):496. doi: 10.1038/s41419-020-2526-9.

Abstract

Chondroitin polymerizing factor (CHPF) is an important member of glycosyltransferases involved in the biosynthesis of chondroitin sulfate (CS). However, the relationship between CHPF and malignant melanoma (MM) is still unknown. In this study, it was demonstrated that CHPF was up-regulated in MM tissues compared with the adjacent normal skin tissues and its high expression was correlated with more advanced T stage. Further investigations indicated that the over-expression/knockdown of CHPF could promote/inhibit proliferation, colony formation and migration of MM cells, while inhibiting/promoting cell apoptosis. Moreover, knockdown of CHPF could also suppress tumorigenicity of MM cells in vivo. RNA-sequencing followed by Ingenuity pathway analysis (IPA) was performed for exploring downstream of CHPF and identified CDK1 as the potential target. Furthermore, our study revealed that knockdown of CDK1 could inhibit development of MM in vitro, and alleviate the CHPF over-expression induced promotion of MM. In conclusion, our study showed, as the first time, CHPF as a tumor promotor for MM, whose function was carried out probably through the regulation of CDK1.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis
  • CDC2 Protein Kinase / metabolism*
  • Carcinogenesis / metabolism
  • Carcinogenesis / pathology
  • Cell Line, Tumor
  • Cell Movement
  • Cell Proliferation
  • Disease Progression
  • Epithelial-Mesenchymal Transition
  • Female
  • Gene Expression Regulation, Neoplastic
  • Gene Knockdown Techniques
  • Humans
  • Male
  • Melanoma / enzymology
  • Melanoma / genetics
  • Melanoma / metabolism*
  • Melanoma / pathology*
  • Middle Aged
  • N-Acetylgalactosaminyltransferases
  • Skin / metabolism
  • Skin / pathology

Substances

  • N-Acetylgalactosaminyltransferases
  • chondroitin synthase
  • CDC2 Protein Kinase
  • CDK1 protein, human