Role of ATG7-dependent non-autophagic pathway in angiogenesis

Abstract

ATG7, one of the core proteins of autophagy, plays an important role in various biological processes, including the regulation of autophagy. While clear that autophagy drives angiogenesis, the role of ATG7 in angiogenesis remains less defined. Several studies have linked ATG7 with angiogenesis, which has long been underappreciated. The knockdown of ATG7 gene in cerebrovascular development leads to angiogenesis defects. In addition, specific knockout of ATG7 in endothelial cells results in abnormal development of neovascularization. Notably, the autophagy pathway is not necessary for ATG7 regulation of angiogenesis, while the ATG7-dependent non-autophagic pathway plays a critical role in the regulation of neovascularization. In order to gain a better understanding of the non-autophagic pathway-mediated biological functions of the autophagy-associated protein ATG7 and to bring attention to this expanding but understudied research area, this article reviews recent developments in the ATG7-dependent non-autophagic pathways regulating angiogenesis.

To eat or not to eat: a critical review on the role of autophagy in prostate carcinogenesis and prostate cancer therapeutics

“…However, the extent to which this is necessary in order to firmly prove causality should not be underestimated. The reason for this is firstly that, as opposed to what was assumed upon their initial identification in the 1990s, most, if not all, ATG proteins have non-autophagic cellular functions ( Yousefi et al, 2006 ; Gan and Guan, 2008 ; Baisamy et al, 2009 ; Hanson et al, 2010 ; DeSelm et al, 2011 ; Chung et al, 2012 ; Lee et al, 2012 ; Velikkakath et al, 2012 ; Maskey et al, 2013 ; Elgendy et al, 2014 ; Rohatgi et al, 2015 ; Chen et al, 2016 ; Joo et al, 2016 ; Joshi et al, 2016 ; Kaizuka and Mizushima, 2016 ; Nunes et al, 2016 ; Yang et al, 2016 ; Guo et al, 2017 ; Ramkumar et al, 2017 ; Wang and Kundu, 2017 ; Cadwell and Debnath, 2018 ; Saleiro et al, 2018 ; Galluzzi and Green, 2019 ; Hu et al, 2020 ; Lindner et al, 2020 ; Wu et al, 2020 ; Fang et al, 2021 ; Li et al, 2021 ; Mailler et al, 2021 ; Nieto-Torres et al, 2021 ; Sun et al, 2021 ; Zhang et al, 2022a ; Hamaoui and Subtil, 2022 ; Rajak et al, 2022 ; Chen et al, 2023 ; Deng et al, 2023 ; Liang et al, 2023 ; Wang et al, 2023 ; Tedesco et al, 2024 ; Tran et al, 2024 ; Yoon et al, 2024 ) that are likely to influence the cellular/phenotypic effects that are observed upon their knockdown, knockout or overexpression, and many of these functions affect pathways that are highly relevant to cancer. Therefore, in order to infer causality, the same cellular/phenotypic effect must be observed upon interference with a number of different ATGs.…”

“…However, before concluding this, it is imperative to examine the effects of depletion of several other ATGs, as well as their effect in different models of prostate cancer. It is important to note that ATG7 has several non-autophagic functions ( DeSelm et al, 2011 ; Lee et al, 2012 ; Chen et al, 2023 ; Deng et al, 2023 ), and in relation to this, an alternative explanation for the delayed development and growth of the Pten deficiency-induced mouse prostate tumours mentioned above ( Santanam et al, 2016 ), could for instance, be related to the autophagy-independent effect that ATG7 has upon binding to the tumour suppressor TP53, which results in enhanced apoptotic cell death in the absence of Atg7 ( Lee et al, 2012 ). It should also be noted that prostate cancer has not been associated with alterations in ATG7 expression or function.…”