Pseudophosphatase STYX promotes tumor growth and metastasis by inhibiting FBXW7 function in colorectal cancer

Cancer Lett. 2019 Jul 10:454:53-65. doi: 10.1016/j.canlet.2019.04.014. Epub 2019 Apr 11.

Abstract

Serine/threonine/tyrosine interacting protein (STYX), a member of protein tyrosine phosphatases, has recently been reported as a potential oncogene. However, the role of STYX in colorectal cancer (CRC) remains unknown. In this study, we found that STYX was highly expressed in CRC tissues and closely correlated with tumor development and survival of CRC patients. In vitro studies showed that overexpression of STYX promoted proliferation, migration, invasion, and epithelial-mesenchymal transition (EMT) and inhibited apoptosis in CRC cells, while STYX knockdown had the opposite effects. Consistently, in vivo experiments showed that overexpression of STYX promoted tumor growth and lung metastasis. Mechanically, STYX bound to the F-box and WD repeat domain-containing7 (FBXW7) protein and inhibited its function. Co-regulation of STYX and FBXW7 expression reversed the biological changes mediated by regulation of STYX expression alone in CRC cells. Additionally, FBXW7 expression was negatively associated with STYX expression in CRC tissues, and low STYX levels accompanying high FBXW7 levels predicted favorable prognosis of CRC patients. In conclusion, our results suggest that STYX plays an oncogenic role by inhibiting FBXW7 and represents a potential therapeutic target and prognostic biomarker in CRC.

Keywords: EMT; Oncogene; Prognostic biomarker; Protein tyrosine phosphatases.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Animals
  • Apoptosis / physiology
  • Cell Growth Processes / physiology
  • Cell Line, Tumor
  • Cell Movement / physiology
  • Colorectal Neoplasms / metabolism*
  • Colorectal Neoplasms / pathology
  • Epithelial-Mesenchymal Transition
  • F-Box-WD Repeat-Containing Protein 7 / antagonists & inhibitors*
  • F-Box-WD Repeat-Containing Protein 7 / metabolism
  • Female
  • HCT116 Cells
  • HT29 Cells
  • Heterografts
  • Humans
  • Intracellular Signaling Peptides and Proteins / biosynthesis
  • Intracellular Signaling Peptides and Proteins / metabolism*
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • Middle Aged
  • Neoplasm Metastasis
  • Up-Regulation

Substances

  • F-Box-WD Repeat-Containing Protein 7
  • FBXW7 protein, human
  • Intracellular Signaling Peptides and Proteins
  • STYX protein, human