Inflammatory signaling cascades and autophagy in cancer

Abstract

Tumor-associated inflammation is predictive of poor prognosis and drives a variety of tumorigenic phenotypes, including tumor proliferation and survival, angiogenesis, invasiveness, and metastasis. Here, we review mammalian data addressing the interaction of macroautophagy/autophagy with key signaling cascades associated with tumor inflammation. Although our understanding of this area remains incomplete, certain inflammatory pathways have emerged as important mediators of the crosstalk between autophagy and inflammation in tumors. Consistent with the multifaceted roles for autophagy in tumor cells, results to date support the hypothesis that inflammatory pathways can suppress or induce autophagy in a context-dependent manner; in turn, autophagy suppresses or promotes inflammation in cancers. Furthermore, emerging data suggest that autophagy may influence cytokine production and secretion via diverse mechanisms, which has implications for the immune and inflammatory microenvironment in tumors.