Upregulated STAT3 and RhoA signaling in colorectal cancer (CRC) regulate the invasion and migration of CRC cells

Eur Rev Med Pharmacol Sci. 2016 May;20(10):2028-37.

Abstract

Objective: We aimed to reveal the expression and activation of signal transducers and activators of transcription 3 (STAT3) and RhoA/Rho-associated coiled-coil forming kinase 1 (ROCK1) signaling in CRC tissues, and to investigate the regulatory role of STAT3 and RhoA signaling in the invasion and migration of colorectal cancer cells.

Materials and methods: We examined the expression of STAT3, RhoA and ROCK1 in CRC tissues with real-time PCR and Western blotting methods. And then we examined the interaction between STAT3 and RhoA/ROCK1 signaling in CRC HT-29 cells with gain-of-function and loss-of-function strategies. In addition, we determined the regulation by STAT3 and RhoA/ROCK1 on the invasion and migration of CRC HT-29 cells.

Results: Our study demonstrated a significant upregulation of RhoA and ROCK1 expression and STAT3-Y705 phosphorylation in 32 CRC specimens, compared to the 17 normal CRC tissues. Further study demonstrated there was a coordination between STAT3 and RhoA/Rock signaling in the HT-29 cells. Moreover, STAT3 knockdown or RhoA knockdown significantly repressed the migration and invasion in HT-29 cells and vice versa.

Conclusions: STAT3 and RhoA signaling regulate the invasion and migration of CRC cells, implying the orchestrated and oncogenic roles of STAT3 and RhoA/ROCK1 signaling in CRC.

MeSH terms

  • Cell Movement
  • Colorectal Neoplasms* / metabolism
  • Colorectal Neoplasms* / pathology
  • Humans
  • Neoplasm Invasiveness
  • STAT3 Transcription Factor / biosynthesis*
  • Signal Transduction
  • rho-Associated Kinases / metabolism
  • rhoA GTP-Binding Protein / metabolism

Substances

  • STAT3 Transcription Factor
  • STAT3 protein, human
  • ROCK1 protein, human
  • rho-Associated Kinases
  • rhoA GTP-Binding Protein