The Role of Beclin 1-Dependent Autophagy in Cancer

Abstract

Autophagy (self-eating) is an intracellular degradation process used by cells to keep a "clean house"; as it degrades abnormal or damaged proteins and organelles, it helps to fight infections and also provides energy in times of fasting or exercising. Autophagy also plays a role in cancer, although its precise function in each cancer type is still obscure, and whether autophagy plays a protecting (through the clearing of damaged organelles and protein aggregates and preventing DNA damage) or a promoting (by fueling the already stablished tumor) role in cancer remains to be fully characterized. Beclin 1, the mammalian ortholog of yeast Atg6/Vps30, is an essential autophagy protein and has been shown to play a role in tumor suppression. Here, an update of the tumorigenesis regulation by Beclin 1-dependent autophagy is provided.

Breast Cancer Chemotherapeutic Options: A General Overview on the Preclinical Validation of a Multi-Target Ruthenium(III) Complex Lodged in Nucleolipid Nanosystems

“…Moreover, Beclin 1 is often reduced in BCs including TNBC, and this could have adverse effects on cancer growth [167,168]. Indeed, the inducer regulatory role of Beclin 1 in the autophagic flux in MCF-7 cells has been linked with cellular proliferation slowdown [169].…”

“…In support of these findings, a few recent data show autophagic machinery defects next to Beclin 1 lack under different circumstances, as well as chemotherapeutic interventions. Moreover, Beclin 1 is often reduced in BCs including TNBC, and this could have adverse effects on cancer growth [ 167 , 168 ]. Indeed, the inducer regulatory role of Beclin 1 in the autophagic flux in MCF-7 cells has been linked with cellular proliferation slowdown [ 169 ].…”

Regulation of Beclin 1-Mediated Autophagy by Oncogenic Tyrosine Kinases

“…Multiple Beclin 1 phosphorylation events have been reported that eventually modulate autophagy activity in mammals, either by induction or inhibition (reviewed in [30,31]), and multiple oncogenic kinases have also been involved in autophagy modulation through Beclin 1 phosphorylation [32]. Phosphorylation at Ser90 has been shown to activate autophagy through several kinases, including MK2/3 [15], DAPK3, [33], calcium-calmodulin-dependent protein kinase type II (CAMKII, [34]), AMP-activated protein kinase (AMPK, [35]), and also by the phosphatase PP2A [33].…”

Dietary Energy Modulation and Autophagy: Exploiting Metabolic Vulnerabilities to Starve Cancer

“…Although human cancers largely lack evidence of genetic inactivation of core autophagy machinery, various murine models have revealed that knockouts of key autophagic genes promote tumorigenesis ( Amaravadi et al, 2016 ). In addition to its role in initiating autophagy ( Vega-Rubín-de-Celis, 2019 ), BECN1 is essential for early embryonic development and regulates growth factor receptor signaling ( Yue et al, 2003 ; Rohatgi and Shaw, 2016 ). As a result, biallelic deletions of BECN1 cannot be studied because of lethality in animal models.…”