Pro-Tumoral Functions of Autophagy Receptors in the Modulation of Cancer Progression

Abstract

Cancer progression involves a variety of pro-tumorigenic biological processes including cell proliferation, migration, invasion, and survival. A cellular pathway implicated in these pro-tumorigenic processes is autophagy, a catabolic route used for recycling of cytoplasmic components to generate macromolecular building blocks and energy, under stress conditions, to remove damaged cellular constituents to adapt to changing nutrient conditions and to maintain cellular homeostasis. During autophagy, cells form a double-membrane sequestering a compartment termed the phagophore, which matures into an autophagosome. Following fusion with the lysosome, the cargo is degraded inside the autolysosomes and the resulting macromolecules released back into the cytosol for reuse. Cancer cells use this recycling system during cancer progression, however the key autophagy players involved in this disease is unclear. Accumulative evidences show that autophagy receptors, crucial players for selective autophagy, are overexpressed during cancer progression, yet the mechanisms whereby pro-tumorigenic biological processes are modulated by these receptors remains unknown. In this review, we summarized the most important findings related with the pro-tumorigenic role of autophagy receptors p62/SQSTM1, NBR1, NDP52, and OPTN in cancer progression. In addition, we showed the most relevant cargos degraded by these receptors that have been shown to function as critical regulators of pro-tumorigenic processes. Finally, we discussed the role of autophagy receptors in the context of the cellular pathways implicated in this disease, such as growth factors signaling, oxidative stress response and apoptosis. In summary, we highlight that autophagy receptors should be considered important players of cancer progression, which could offer a niche for the development of novel diagnosis and cancer treatment strategies.

The regulation, function, and role of lipophagy, a form of selective autophagy, in metabolic disorders

“…1 ). Rab10 recruits LC3-positive autophagy membranes to LDs and promotes the phagocytosis of LDs into autophagosomes by binding to adaptor protein EH domain binding protein 1 (EHBP1) and membrane deformed ATP EH domain-containing 2 (EHD2) to form a complex [ 59 ], which is essential to lipophagy in hepatocytes. The selective autophagy of organelles involves specific receptors that initiate autophagy around the organelle by binding to LC3.…”

The role of LncRNA-mediated autophagy in cancer progression

“…p62 is made up of 440 amino acids and has a multitude of structural domains with different functions. From the N-terminal to the C-segment, they are Phox-BEM1 structural domain (PB1), ZZ-type zinc finger structural domain, nuclear localization signal 1 (NLS1), tumor necrosis factor receptor-associated factor 6-binding (TRAF6-binding) TB domain, nuclear localization signal 1 (NLS2), export motif (NES), and LC3 interaction region (LIR), Keap1 interaction region (KIR) and ubiquitin-associated structural domain (UBA) ( Liu et al, 2016 ; Cerda-Troncoso et al, 2020 ).…”

Construction and validation of an autophagy-related long non-coding RNA signature to predict the prognosis of kidney renal papillary cell carcinoma

“…Autophagy, known as the gene-related endogenous autophagy, is under the strict control of highly adaptive cell metabolic process itself, and is responsible for aggregation, degradation, and recycling of the damaged or dysfunctional organelles and protein to adapt to changes of nutritional environment and maintain cell steady state, which is the important mechanism for the cell development, differentiation, and survival. 8 Cancer cells, under stress conditions, can use this autophagy process to generate alternative energy through nutrient recycling, but excessive activation of autophagy might cause cancer cells death. 9 Autophagy is also closely related to RCC.…”