Silencing of FOXO6 inhibits the proliferation, invasion, and glycolysis in colorectal cancer cells

J Cell Biochem. 2019 Mar;120(3):3853-3860. doi: 10.1002/jcb.27667. Epub 2018 Oct 15.

Abstract

Forkhead box class O6 (FOXO6) is an important member of FOXO family, which has been demonstrated to be implicated in tumor development. However, the role of FOXO6 in colorectal cancer (CRC) is still unclear. The study aimed to investigate the potential roles of FOXO6 in the development of CRC. Our results showed that FOXO6 was overexpressed in CRC tissues and cell lines. FOXO6 knockdown inhibited cell proliferation, as well as repressed the migration and invasion of CRC cells. Additionally, we found that FOXO6 knockdown altered cellular metabolism by inhibiting glycolysis and promoting mitochondrial respiration. Furthermore, FOXO6 knockdown inhibited the activation of PI3K/Akt/mTOR pathway in CRC cells. The results herein indicated that FOXO6 knockdown inhibited cell proliferation, migration, invasion, and glycolysis in CRC cells. PI3K/Akt/mTOR pathway was involved in the effects of FOXO6 on CRC cells. These findings suggested that FOXO6 might be a potential target for the CRC therapy.

Keywords: PI3K/Akt/mTOR pathway; colorectal cancer; extracellular acidification rate; forkhead box class O6; glycolysis; oxygen consumption rate.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Caco-2 Cells
  • Cell Movement / drug effects
  • Cell Proliferation / drug effects
  • Cell Survival
  • Colorectal Neoplasms / genetics*
  • Colorectal Neoplasms / metabolism
  • Colorectal Neoplasms / pathology
  • Colorectal Neoplasms / surgery
  • Forkhead Transcription Factors / antagonists & inhibitors
  • Forkhead Transcription Factors / genetics*
  • Forkhead Transcription Factors / metabolism
  • Gene Expression Regulation, Neoplastic*
  • Glucose / pharmacology
  • Glycolysis / drug effects
  • Glycolysis / genetics
  • HCT116 Cells
  • HT29 Cells
  • Humans
  • Neoplasm Invasiveness
  • Oligomycins / pharmacology
  • Oxidative Phosphorylation / drug effects
  • Oxygen Consumption / drug effects
  • Oxygen Consumption / genetics
  • Phosphatidylinositol 3-Kinases / genetics*
  • Phosphatidylinositol 3-Kinases / metabolism
  • Proto-Oncogene Proteins c-akt / genetics*
  • Proto-Oncogene Proteins c-akt / metabolism
  • RNA, Small Interfering / genetics
  • RNA, Small Interfering / metabolism
  • Signal Transduction
  • TOR Serine-Threonine Kinases / genetics*
  • TOR Serine-Threonine Kinases / metabolism

Substances

  • FOXO6 protein, human
  • Forkhead Transcription Factors
  • Oligomycins
  • RNA, Small Interfering
  • MTOR protein, human
  • Proto-Oncogene Proteins c-akt
  • TOR Serine-Threonine Kinases
  • Glucose