Targeting autophagy and beyond: Deconvoluting the complexity of Beclin-1 from biological function to cancer therapy

Jing Ye; Jin Zhang; Yanghui Zhu; Lian Wang; Xian Jiang; Bo Liu; Gu He

doi:10.1016/j.apsb.2023.08.008

Targeting autophagy and beyond: Deconvoluting the complexity of Beclin-1 from biological function to cancer therapy

Acta Pharm Sin B. 2023 Dec;13(12):4688-4714. doi: 10.1016/j.apsb.2023.08.008. Epub 2023 Aug 12.

Authors

Jing Ye¹, Jin Zhang¹, Yanghui Zhu¹, Lian Wang^{1

2}, Xian Jiang¹, Bo Liu¹, Gu He^{1

2}

Affiliations

¹ Department of Dermatology, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu 610041, China.
² Laboratory of Dermatology, Clinical Institute of Inflammation and Immunology (CIII), Frontiers Science Center for Disease Related Molecular Network, Chengdu 610041, China.

Abstract

Beclin-1 is the firstly-identified mammalian protein of the autophagy machinery, which functions as a molecular scaffold for the assembly of PI3KC3 (class III phosphatidylinositol 3 kinase) complex, thus controlling autophagy induction and other cellular trafficking events. Notably, there is mounting evidence establishing the implications of Beclin-1 in diverse tumorigenesis processes, including tumor suppression and progression as well as resistance to cancer therapeutics and CSC (cancer stem-like cell) maintenance. More importantly, Beclin-1 has been confirmed as a potential target for the treatment of multiple cancers. In this review, we provide a comprehensive survey of the structure, functions, and regulations of Beclin-1, and we discuss recent advances in understanding the controversial roles of Beclin-1 in oncology. Moreover, we focus on summarizing the targeted Beclin-1-regulating strategies in cancer therapy, providing novel insights into a promising strategy for regulating Beclin-1 to improve cancer therapeutics in the future.

Keywords: Autophagy; Beclin-1; Cancer therapy; Non-autophagy; PI3KC3 complex.

Publication types

Review