The Regulatory Mechanisms of Dynamin-Related Protein 1 in Tumor Development and Therapy

Abstract

Background: Various types of tumors are likely to acquire drug resistance over time. Hence, the development of novel therapies to overcome drug resistance is critical. Studies have demonstrated that drug resistance is closely associated with the dynamic regulation of mitochondria in tumor cells. The dynamin-related protein 1 (Drp1) is involved in the regulation of mitochondrial fission and plays an important role in maintaining mitochondrial morphology, function, and distribution. It is a key protein in mitochondrial quality control. Drp1 is a GTPase localized to the cytoplasm and is a potential target in cancer therapy. A variety of drugs targeting Drp1 have shown great promise in reducing the viability and proliferation of cancer cells. The dynamic regulation of Drp1-mediated mitochondria is closely associated with tumor development, and treatment. Aim: In this article, the authors reviewed the occurrence and progression of mitochondrial fission regulated by Drp1, and its influence on cell cycle, autophagy, apoptosis, migration, invasion, the molecular mechanism of tumor stemness, and metabolic reprogramming. Targeted inhibition of Drp1 and mitochondrial fission could reduce or prevent tumor occurrence and progression in a variety of cancers. Drp1 inhibitors could reduce tumor stemness and enhance tumor sensitivity to chemotherapeutic drugs. Conclusion: Research into identifying compounds that could specifically target Drp1 will be valuable for overcoming drug resistance in tumors.

Keywords: antitumor effects; apoptosis; dynamin-related protein 1 (Drp1); invasion and migration; mitophagy; targeted drugs.