Supplementary Figure 5 from Targeting Protein Synthesis in a Myc/mTOR-Driven Model of Anorexia-Cachexia Syndrome Delays Its Onset and Prolongs Survival

Robert, Francis; Mills, John R.; Agenor, Aouod; Wang, Dantong; DiMarco, Sergio; Cencic, Regina; Tremblay, Michel L.; Gallouzi, Imed Eddine; Hekimi, Siegfried; Wing, Simon S.; Pelletier, Jerry

doi:10.1158/0008-5472.22392912.v1

Supplementary Figure 5 from Targeting Protein Synthesis in a Myc/mTOR-Driven Model of Anorexia-Cachexia Syndrome Delays Its Onset and Prolongs Survival

journal contribution

posted on 2023-03-30, 21:10 authored by Francis Robert, John R. Mills, Aouod Agenor, Dantong Wang, Sergio DiMarco, Regina Cencic, Michel L. Tremblay, Imed Eddine Gallouzi, Siegfried Hekimi, Simon S. Wing, Jerry Pelletier

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ARTICLE ABSTRACT

Anorexia-cachexia syndrome (ACS) is a major determinant of cancer-related death that causes progressive body weight loss due to depletion of skeletal muscle mass and body fat. Here, we report the development of a novel preclinical murine model of ACS in which lymphomas harbor elevated Myc and activated mTOR signaling. The ACS phenotype in this model correlated with deregulated expression of a number of cytokines, including elevated levels of interleukin-10 which was under the direct translational control of mTOR. Notably, pharmacologic intervention to impair protein synthesis restored cytokine production to near-normal levels, delayed ACS progression, and extended host survival. Together, our findings suggest a new paradigm to treat ACS by strategies which target protein synthesis to block the production of procachexic factors. Cancer Res; 72(3); 747–56. ©2011 AACR.