Crosstalk between autophagy and epithelial-mesenchymal transition and its application in cancer therapy

Abstract

Autophagy is a highly conserved catabolic process that mediates degradation of pernicious or dysfunctional cellular components, such as invasive pathogens, senescent proteins, and organelles. It can promote or suppress tumor development, so it is a “double-edged sword” in tumors that depends on the cell and tissue types and the stages of tumor. The epithelial-mesenchymal transition (EMT) is a complex biological trans-differentiation process that allows epithelial cells to transiently obtain mesenchymal features, including motility and metastatic potential. EMT is considered as an important contributor to the invasion and metastasis of cancers. Thus, clarifying the crosstalk between autophagy and EMT will provide novel targets for cancer therapy. It was reported that EMT-related signal pathways have an impact on autophagy; conversely, autophagy activation can suppress or strengthen EMT by regulating various signaling pathways. On one hand, autophagy activation provides energy and basic nutrients for EMT during metastatic spreading, which assists cells to survive in stressful environmental and intracellular conditions. On the other hand, autophagy, acting as a cancer-suppressive function, is inclined to hinder metastasis by selectively down-regulating critical transcription factors of EMT in the early phases. Therefore, the inhibition of EMT by autophagy inhibitors or activators might be a novel strategy that provides thought and enlightenment for the treatment of cancer. In this article, we discuss in detail the role of autophagy and EMT in the development of cancers, the regulatory mechanisms between autophagy and EMT, the effects of autophagy inhibition or activation on EMT, and the potential applications in anticancer therapy.

Long non-coding RNA HAL suppresses the migration and invasion of serous ovarian cancer by inhibiting EMT signaling pathway

“…Epithelial-mesenchymal transition (EMT) refers to the epithelial cells transforming into mesenchymal cells, thereby gaining the process of interstitial cell phenotype [15]. EMT was reported to be involved in embryonic development, tissue remodeling, wound healing, tumor metastasis and other pathological physiological process [16].…”

Therapeutic Potential of Autophagy Modulation in Cholangiocarcinoma

“…The link between EMT and autophagy has been amply demonstrated, since main pathways regulating autophagy have a dramatic impact on EMT, such as PI3K/AKT/mTOR, Beclin1, p53 and JAK/STAT signaling pathways. Additionally, signaling pathways implicated in EMT are crucial in autophagy, including integrins, WNTs, NF-kB, and TGF-β signaling pathways [123]. In CCA, EMT leads to immunosuppression through SNAIL expression [124] and is critical for invasiveness and metastasis induced by TGF-β1/SNAIL activation [125].…”

The importance of epithelial-mesenchymal transition and autophagy in cancer drug resistance

“…The signalling pathways of both EMT and autophagy are complex and can be induced in a number of ways; it is therefore unsurprising that there is some interaction between these two pathways [36,37] . Numerous studies in different contexts have demonstrated interactions between autophagy and EMT, although it does appear this is both context-and tissue-dependent [ Table 1].…”