TTK regulates proliferation and apoptosis of gastric cancer cells through the Akt-mTOR pathway

FEBS Open Bio. 2020 Aug;10(8):1542-1549. doi: 10.1002/2211-5463.12909. Epub 2020 Jul 1.

Abstract

TTK (also known as Mps1) is the core component of the spindle assembly checkpoint, which ensures proper distribution of chromosomes to daughter cells to maintain genome integrity and to balance growth and division. However, the function of TTK in tumorigenesis has not been extensively studied, especially in relation to the development of gastric cancer. In this study, survival and tumor recurrence data related to TTK expression level in gastric cancer patients were collected and analyzed. We observed that TTK expression was negatively correlated with survival and tumor recurrence in vivo. TTK was also upregulated in gastric cancer cells and was observed to be essential for the proliferation and survival of gastric cancer cells. Knockdown of TTK inhibited proliferation and increased apoptosis. Furthermore, we report that TTK regulates the proliferation and apoptosis of tumor cells through the Akt-mTOR pathway. Knockdown of TTK inhibited activation of Akt-mTOR signaling. In summary, our data indicate that TTK is involved in the regulation of gastric cancer proliferation and apoptosis.

Keywords: Akt-mTOR pathway; TTK; apoptosis; gastric cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis*
  • Cell Cycle Proteins / metabolism*
  • Cell Proliferation
  • Humans
  • Protein Serine-Threonine Kinases / metabolism*
  • Protein-Tyrosine Kinases / metabolism*
  • Proto-Oncogene Proteins c-akt / metabolism*
  • Stomach Neoplasms / metabolism*
  • Stomach Neoplasms / pathology
  • TOR Serine-Threonine Kinases / metabolism*
  • Tumor Cells, Cultured

Substances

  • Cell Cycle Proteins
  • MTOR protein, human
  • Protein-Tyrosine Kinases
  • Protein Serine-Threonine Kinases
  • Proto-Oncogene Proteins c-akt
  • TOR Serine-Threonine Kinases
  • TTK protein, human