期刊
SEMINARS IN CANCER BIOLOGY
卷 66, 期 -, 页码 89-100出版社
ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
DOI: 10.1016/j.semcancer.2019.03.002
关键词
Autophagy; Ferroptosis; Iron; Lipid peroxidation; Cell death
类别
资金
- US National Institutes of Health [R01CA160417, R01CA211070, GM053396]
- American Cancer Society [RSG-16-014-01-CDD]
- National Natural Science Foundation of China [81570154]
- Ligue contre le Cancer (equipe labellisee)
- Agence National de la Recherche (ANR) - Projets blancs
- ANR
- Association pour la recherche sur le cancer (ARC)
- Canceropole Ile-de-France
- Chancelerie des universites de Paris (Legs Poix), Fondation pour la Recherche Medicale (FRM)
- European Research Area Network on Cardiovascular Diseases (ERA-CVD, MINOTAUR)
- European Union Horizon 2020 Project Oncobiome
- Fondation Carrefour
- Institut National du Cancer (INCa)
- Inserm (HTE)
- Institut Universitaire de France
- LeDucq Foundation
- LabEx ImmunoOncology
- RHU Torino Lumiere
- Seerave Foundation
- SIRIC Stratified Oncology Cell DNA Repair and Tumor Immune Elimination (SOCRATE)
- SIRIC Cancer Research and Personalized Medicine (CARPEM)
Macroautophagy (hereafter referred to as autophagy) involves an intracellular degradation and recycling system that, in a context-dependent manner, can either promote cell survival or accelerate cellular demise. Ferroptosis was originally defined in 2012 as an iron-dependent form of cancer cell death different from apoptosis, necrosis, and autophagy. However, this latter assumption came into question because, in response to ferroptosis activators (e.g., erastin and RSL3), autophagosomes accumulate, and because components of the autophagy machinery (e.g., ATG3, ATG5, ATG4B, ATG7, ATG13, and BECN1) contribute to ferroptotic cell death. In particular, NCOA4-facilitated ferritinophagy, RAB7A-dependent lipophagy, BECN1-mediated system x(c)(-) inhibition, STAT3-induced lysosomal membrane permeabilization, and HSP90-associated chaperone-mediated autophagy can promote ferroptosis. In this review, we summarize current knowledge on the signaling pathways involved in ferroptosis, while focusing on the regulation of autophagy-dependent ferroptotic cell death. The molecular comprehension of these phenomena may lead to the development of novel anticancer therapies.
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