STK33/ERK2 signal pathway contribute the tumorigenesis of colorectal cancer HCT15 cells

Biosci Rep. 2019 Mar 1;39(3):BSR20182351. doi: 10.1042/BSR20182351. Print 2019 Mar 29.

Abstract

Serine/threonine kinase 33 (STK33) is a serine/threonine kinase and participates in many apoptotic process. Herein, we found that the extracellular signal-regulated kinase 2 (ERK2) was a substrate of STK33. STK33 phosphorylated ERK2 and increased the activity of ERK2 and promote the tumorigenesis of colorectal cancer HCT15 cells. Clinical simple showed that STK33 was highly expression in colorectal cells and tissues. Ex vivo and in vivo studies demonstrated that STK33 accelerate tumorigenic properties in NCM460 cells and athymic nude rats. In vitro kinase assay results indicated that STK33 can phosphorylate ERK2. Ex vivo studies further showed that STK33 can bind with ERK2 and take part in the regulation of ERKs signaling pathway. In short, our results showed that STK33 is a novel upstream kinase of ERK2. It may provide a better prospect for STK33 based prevention and treatment for colorectal cancer patients.

Keywords: ERK2; HCT15; STK33; colorectal cancer; tumorigenesis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Carcinogenesis / genetics
  • Carcinogenesis / metabolism*
  • Cell Line
  • Cell Line, Tumor
  • Colorectal Neoplasms / genetics
  • Colorectal Neoplasms / metabolism*
  • Colorectal Neoplasms / therapy
  • HEK293 Cells
  • Humans
  • MAP Kinase Signaling System / genetics
  • Male
  • Mice, Inbred BALB C
  • Mice, Nude
  • Mitogen-Activated Protein Kinase 1 / metabolism*
  • Phosphorylation
  • Protein Serine-Threonine Kinases / genetics
  • Protein Serine-Threonine Kinases / metabolism*
  • RNA Interference
  • RNAi Therapeutics / methods
  • Xenograft Model Antitumor Assays / methods

Substances

  • Protein Serine-Threonine Kinases
  • STK33 protein, human
  • Mitogen-Activated Protein Kinase 1