Cancer cachexia overrides sex-specific traits in Drosophila

Abstract

Cancer cachexia, a metabolic syndrome characterized by pathologic weight loss, dramatically limits therapeutic options and reduces survival. While the mechanisms by which tumors induce wasting of distant organs (particularly muscle and adipose tissues) remain incompletely understood, the influence of biological sex on cachexia progression is even less clear. Here we investigated phenotypic and molecular manifestations of cachexia in both sexes using a model of inducible intestinal tumors in Drosophila. We show that tumor progression leads to the development of severe cachexia both in males and in females manifested by organ atrophies and an inflammatory state. Nevertheless, both phenotypical and molecular cachexic alterations exhibit striking differences between sexes. Transcriptomic analysis show that many genes differentially expressed at high levels in males under normal conditions become downregulated during cachexia, while their expression is upregulated in cachexic females, and reciprocally. Together, sex-specific deregulation in gene expression and metabolic profiles ultimately converge towards a molecular cachexic state that erase or diminish many sex-specific differences otherwise characteristic of healthy males and females. These findings highlight the interplay between oncogenic stress and biological sex in shaping cachexia phenotypes, shedding light on how sex influences the development of cancer cachexia.