LYRM2 directly regulates complex I activity to support tumor growth in colorectal cancer by oxidative phosphorylation

Cancer Lett. 2019 Jul 28;455:36-47. doi: 10.1016/j.canlet.2019.04.021. Epub 2019 Apr 17.

Abstract

Oxidative phosphorylation (OXPHOS) in cancer has attracted a considerable attention in the past decades, and accumulated evidence has suggested that it plays an important role in tumor proliferation, metastasis and drug resistance. However, the mechanisms involved in these effects are still ambiguous to date. In this study, we found that LYR motif containing 2 (LYRM2), a novel molecule, is up-regulated in colorectal cancer and promotes tumor growth both in vivo and in vitro. Furthermore, we discovered that LYRM2 locates in the mitochondria, directly interacts with complex I and increases its activity, thus promoting OXPHOS in colorectal cancer cells. More importantly, we identified a new Akt-S58phos-LYRM2-Complex I axis, which is responsible for the LYRM2-induced tumor growth and the activation of OXPHOS in colorectal cancer. Our finding illustrates the role of LYRM2 in regulating tumor metabolism and provides a new potential target for colorectal cancer treatment.

Keywords: AKT; Cancer proliferation; Complex I; ECT; LYRM2; OXPHOS.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Growth Processes / physiology
  • Colorectal Neoplasms / metabolism*
  • Colorectal Neoplasms / pathology
  • Electron Transport Complex I / metabolism*
  • HEK293 Cells
  • Heterografts
  • Humans
  • Male
  • Mice
  • Mice, Nude
  • Mitochondrial Membranes / metabolism
  • Mitochondrial Membranes / pathology
  • Mitochondrial Proteins / metabolism*
  • Oxidative Phosphorylation
  • Proto-Oncogene Proteins c-akt / metabolism
  • Up-Regulation

Substances

  • LYRM2 protein, human
  • Mitochondrial Proteins
  • Proto-Oncogene Proteins c-akt
  • Electron Transport Complex I