4.7 Article

Role and regulation of autophagy in cancer

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ELSEVIER
DOI: 10.1016/j.bbadis.2022.166400

Keywords

Autophagy; Homeostasis; Cancer; Hypoxia

Funding

  1. Department of Health Research [12014/11/2018-HR/E-of-fice:3151264]

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Autophagy is a significant mechanism related to cellular stress, metabolism, and cancer, but its role in cancer is still not well understood. Autophagy involves modifications of various proteins and pathways and is influenced by the interaction between tumor cells and their microenvironment.
Autophagy is an intracellular self-degradative mechanism which responds to cellular conditions like stress or starvation and plays a key role in regulating cell metabolism, energy homeostasis, starvation adaptation, development and cell death. Numerous studies have stipulated the participation of autophagy in cancer, but the role of autophagy either as tumor suppressor or tumor promoter is not clearly understood. However, mechanisms by which autophagy promotes cancer involves a diverse range of modifications of autophagy associated proteins such as ATGs, Beclin-1, mTOR, p53, KRAS etc. and autophagy pathways like mTOR, PI3K, MAPK, EGFR, HIF and NF kappa B. Furthermore, several researches have highlighted a context-dependent, cell type and stage-dependent regulation of autophagy in cancer. Alongside this, the interaction between tumor cells and their microenvironment including hypoxia has a great potential in modulating autophagy response in favour to substantiate cancer cell metabolism, self-proliferation and metastasis. In this review article, we highlight the mechanism of autophagy and their contribution to cancer cell proliferation and development. In addition, we discuss about tumor microenvironment interaction and their consequence on selective autophagy pathways and the involvement of autophagy in various tumor types and their therapeutic interventions concentrated on exploiting autophagy as a potential target to improve cancer therapy.

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