Involvement of Actin in Autophagy and Autophagy-Dependent Multidrug Resistance in Cancer

Abstract

Currently, autophagy in the context of cancer progression arouses a lot of controversy. It is connected with the possibility of switching the nature of this process from cytotoxic to cytoprotective and vice versa depending on the treatment. At the same time, autophagy of cytoprotective character may be one of the factors determining multidrug resistance, as intensification of the process is observed in patients with poorer prognosis. The exact mechanism of this relationship is not yet fully understood; however, it is suggested that one of the elements of the puzzle may be a cytoskeleton. In the latest literature reports, more and more attention is paid to the involvement of actin in the autophagy. The role of this protein is linked to the formation of autophagosomes, which are necessary element of the process. However, based on the proven effectiveness of manipulation of the actin pool, it seems to be an attractive alternative in breaking autophagy-dependent multidrug resistance in cancer.

The Synthetic Flavonoid Derivative GL-V9 Induces Apoptosis and Autophagy in Cutaneous Squamous Cell Carcinoma via Suppressing AKT-Regulated HK2 and mTOR Signals

“…Instead, inhibition of autophagy by 3-MA promoted the apoptosis induced by GL-V9, which may be explained by the influences of autophagy in apoptotic signals. Some studies report that the clear of apoptosis cell by autophagy is a selective mechanism for cancer cells, which can help cancer cells overcoming the death stress caused by chemotherapy and result in drug resistance [54,55]. Therefore, the further studies of GL-V9 in cancer treatment should take into account of the double effects of apoptosis and autophagy.…”

The Role of TRPM2 in Endothelial Function and Dysfunction

“…Thus, the TRPM2-dependent influx of calcium ions appears to have a broad effect on the circulatory system. However, in the case of autophagy, the matter remains controversial as it can be cytoprotective or act as a cell death mechanism [ 40 ].…”

FV-429 induces autophagy blockage and lysosome-dependent cell death of T-cell malignancies via lysosomal dysregulation

“…Although the cell demise induced by autophagy is recognized, in general, the cancer cells tend to activate autophagy for self-rescue and maintaining homeostasis under stress condition 5 – 7 . Increasing studies have implicated that the role of protective autophagy participates in the development of multidrug resistance and protects cancer cells from chemotherapeutics or radiotherapy, suggesting that targeting the protective autophagy process is regarded as a novel therapeutic approach 8 , 9 .…”