Autophagy and ncRNAs: Dangerous Liaisons in the Crosstalk between the Tumor and Its Microenvironment

Abstract

Autophagy is a fundamental cellular homeostasis mechanism known to play multifaceted roles in the natural history of cancers over time. It has recently been shown that autophagy also mediates the crosstalk between the tumor and its microenvironment by promoting the export of molecular payloads such as non-coding RNA (ncRNAs) via LC3-dependent Extracellular Vesicle loading and secretion (LDELS). In turn, the dynamic exchange of exosomal ncRNAs regulate autophagic responses in the recipient cells within the tumor microenvironment (TME), for both tumor and stromal cells. Autophagy-dependent phenotypic changes in the recipient cells further enhance tumor growth and metastasis, through diverse biological processes, including nutrient supplementation, immune evasion, angiogenesis, and therapeutic resistance. In this review, we discuss how the feedforward autophagy-ncRNA axis orchestrates vital communications between various cell types within the TME ecosystem to promote cancer progression.

FGF19 promotes cell autophagy and cisplatin chemoresistance by activating MAPK signaling in ovarian cancer

“…IL-6 activates autophagy through the upregulating JAK2 pathway and promotes chemotherapy resistance in colorectal cancer ( Hu et al, 2021 ). Furthermore, as promising regulators of autophagy, the non-coding RNAs, such as lncRNAs and miRNAs, can regulate therapeutic resistance in cancer cells ( Eng et al, 2021 ; Hou, Li & Dong, 2021 ; Xia et al, 2022 ). Moreover, increasing studies have confirmed that autophagy is involved in the progression and drug resistance of ovarian cancer cells ( Zhao et al, 2021 ).…”