The concerted action of oncogenic driver mutations directs global translation in intestinal epithelial cells

Wouter Smit; Jarom Heijmans

doi:10.1080/23723556.2021.1879614

The concerted action of oncogenic driver mutations directs global translation in intestinal epithelial cells

Mol Cell Oncol. 2021 May 19;8(4):1879614. doi: 10.1080/23723556.2021.1879614. eCollection 2021.

Authors

Wouter Smit¹, Jarom Heijmans^{1

2}

Affiliations

¹ Department of Gastroenterology and Hepatology, Tytgat Institute for Liver and Intestinal Research, Amsterdam University Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
² Department of Internal Medicine and Hematology, Amsterdam University Medical Center, University of Amsterdam, Amsterdam, The Netherlands.

Abstract

Oncogenic transformation of colorectal cancer cells is driven by a set of mutations that cause aberrant signaling of growth factor-receptor pathways. Using organoids, we demonstrate that the most frequent driver mutations in APC, KRAS, SMAD4, and TP53 are enhancers of the global mRNA translational capacity, which is linked to intestinal cell growth in an mTOR-dependent manner.

Keywords: Colorectal cancer; driver mutations; global translation; mTOR signaling; protein synthesis.

Grants and funding

This work was supported by the KWF Kankerbestrijding (NL) [11053/2017- 1].