Interplay Between Autophagy and Wnt/β-Catenin Signaling in Cancer: Therapeutic Potential Through Drug Repositioning

Abstract

The widespread dysregulation that characterizes cancer cells has been dissected and many regulation pathways common to multiple cancer types have been described in depth. Wnt/β-catenin signaling and autophagy are among these principal pathways, which contribute to tumor growth and resistance to anticancer therapies. Currently, several therapeutic strategies that target either Wnt/β-catenin signaling or autophagy are in various stages of development. Targeted therapies that block specific elements that participate in both pathways; are subject to in vitro studies as well as pre-clinical and early clinical trials. Strikingly, drugs designed for other diseases also impact these pathways, which is relevant since they are already FDA-approved and sometimes even routinely used in the clinic. The main focus of this mini-review is to highlight the importance of drug repositioning to inhibit the Wnt/β-catenin and autophagy pathways, with an emphasis on the interplay between them. The data we found strongly suggested that this field is worth further examination.

Is targeting autophagy mechanism in cancer a good approach? The possible double-edge sword effect

“…Besides that, a regulatory feedback between autophagy and Wnt/β-catenin signalling has been reported [ 51 ]. β-catenin negatively modulates autophagy by reducing autophagosome formation and LC3-II puncta during starvation and nutrient-rich conditions [ 52 ].…”

A novel focal adhesion related gene signature for prognostic prediction in hepatocellular carcinoma

“…The Wnt signaling pathway is severely dysregulated in solid and non-solid malignant tumors, acting as part of the proliferation pathway that characterizes cancer cells [ 42 ]. Pérez-Plasencia et al reported that the Wnt signaling pathway, as a common pathway in many cancer types, was a main attractive target in cancer therapy [ 43 ], including HCC [ 35 ]. Dysregulation of the MAPK cascade is linked to some key signaling components and phosphorylation events which can activate the process of tumorigenesis [ 44 ].…”

Construction and Validation of an Autophagy-Related Prognostic Model for Osteosarcoma Patients

“…is was also in line with the "double-edged" role of autophagy mentioned previously [21] which promoted the growth of tumor cells after tumorigenesis. Additionally, previous studies have revealed the close-knit relationship between autophagy and Wnt pathway in OS and other cancers [55,[58][59][60]. Tao et al reported that activation of Wnt pathway represses the expression of Beclin 1, a pivotal element for autophagic flux [61].…”

“…Integrating these results, we concluded that dysregulation of Wnt pathway may mediate the contrition of prognostic AGRs to the prognosis of OS patient. Wnt pathway was a crucial cascade involved in stemness and development, and aberrant Wnt pathway was usually implicated in tumorigenesis and progression [ 55 , 56 ]. It has been proved that there was a dual feedback regulation between Wnt pathway and autophagy [ 57 ], and GSVA analysis revealed that the negative regulation of autophagy was also hindered in the high-risk group in this study.…”