Arginine starvation in colorectal carcinoma cells: Sensing, impact on translation control and cell cycle distribution

Bozhena O. Vynnytska-Myronovska, Yuliya Kurlishchuk, Oleh Chen, Yaroslav Bobak, Claudia Dittfeld, Melanie Hüther, Leoni A. Kunz-Schughart, Oleh V. Stasyk*

*Corresponding author for this work

Research output: Contribution to journalArticleResearchpeer-review

12 Citations (Scopus)

Abstract

Tumor cells rely on a continued exogenous nutrient supply in order to maintain a high proliferative activity. Although a strong dependence of some tumor types on exogenous arginine sources has been reported, the mechanisms of arginine sensing by tumor cells and the impact of changes in arginine availability on translation and cell cycle regulation are not fully understood. The results presented herein state that human colorectal carcinoma cells rapidly exhaust the internal arginine sources in the absence of exogenous arginine and repress global translation by activation of the GCN2-mediated pathway and inhibition of mTOR signaling. Tumor suppressor protein p53 activation and G1/G0 cell cycle arrest support cell survival upon prolonged arginine starvation. Cells with the mutant or deleted TP53 fail to stop cell cycle progression at defined cell cycle checkpoints which appears to be associated with reduced recovery after durable metabolic stress triggered by arginine withdrawal.

Original languageEnglish
Pages (from-to)67-74
Number of pages8
JournalExperimental Cell Research
Volume341
Issue number1
DOIs
Publication statusPublished - 1 Feb 2016
Externally publishedYes

Keywords

  • Arginine starvation
  • Colorectal carcinoma
  • GCN2 pathway
  • Intracellular arginine level
  • MTOR signaling
  • P53 status

Fingerprint

Dive into the research topics of 'Arginine starvation in colorectal carcinoma cells: Sensing, impact on translation control and cell cycle distribution'. Together they form a unique fingerprint.

Cite this