The Biological Role and Clinical Significance of BECLIN-1 in Cancer

Abstract

BECLIN-1 is a multidomain protein that, through dynamic interaction with a variety of partners, controls autophagy and apoptosis, two processes dysregulated in cancer cells, thus playing a crucial role in cell fate. Although mutations in the BECN1 gene are rare in cancer, its frequent monoallelic deletion contributes to spontaneous cancer initiation by impairing autophagy, establishing it as a haploinsufficient tumor suppressor gene. The expression and activity of BECLIN-1 are further modulated by epigenetic mechanisms, alternative splicing, post-translational modifications, and alternative partner interactions. These layers of regulation critically affect the autophagy response, with an impact on cell proliferation, motility, and resistance to multiple stress stimuli. In this review article we outline the structural and functional properties of BECLIN-1 and discuss how its altered expression and protein–protein interactions can be harnessed for diagnostic and therapeutic purposes in cancer.