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Li J, Liu J, Xu Y, et al. Tumor heterogeneity in autophagy-dependent ferroptosis. Autophagy. 2021;17(11):3361-3374doi: 10.1080/15548627.2021.1872241.
Li, J., Liu, J., Xu, Y., Wu, R., Chen, X., Song, X., Zeh, H., Kang, R., Klionsky, D. J., Wang, X., & Tang, D. (2021). Tumor heterogeneity in autophagy-dependent ferroptosis. Autophagy, 17(11), 3361-3374. https://doi.org/10.1080/15548627.2021.1872241
Li, Jingbo, et al. "Tumor heterogeneity in autophagy-dependent ferroptosis." Autophagy vol. 17,11 (2021): 3361-3374. doi: https://doi.org/10.1080/15548627.2021.1872241
Li J, Liu J, Xu Y, Wu R, Chen X, Song X, Zeh H, Kang R, Klionsky DJ, Wang X, Tang D. Tumor heterogeneity in autophagy-dependent ferroptosis. Autophagy. 2021 Nov;17(11):3361-3374. doi: 10.1080/15548627.2021.1872241. Epub 2021 Jan 15. PMID: 33404288; PMCID: PMC8632302.
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Autophagy. 2021 Nov;17(11):3361-3374. doi: 10.1080/15548627.2021.1872241. Epub 2021 Jan 15.

Tumor heterogeneity in autophagy-dependent ferroptosis.

Autophagy

Jingbo Li, Jiao Liu, Yinghua Xu, Runliu Wu, Xin Chen, Xinxin Song, Herbert Zeh, Rui Kang, Daniel J Klionsky, Xiaoyan Wang, Daolin Tang

Affiliations

  1. Department of Surgery, UT Southwestern Medical Center, Dallas, Texas, USA.
  2. Department of Gastroenterology, Third Xiangya Hospital, Central South University, Changsha, Hunan, China.
  3. The Third Affiliated Hospital, Guangzhou Medical University, Guangzhou, Guangdong, China.
  4. Life Sciences Institute and Department of Molecular Cellular and Developmental Biology, University of Michigan, Ann Arbor, Michigan, USA.

PMID: 33404288 PMCID: PMC8632302 DOI: 10.1080/15548627.2021.1872241

Abstract

Macroautophagy (hereafter referred to as "autophagy") is a lysosome-mediated degradation process that plays a complex role in cellular stress, either promoting survival or triggering death. Early studies suggest that ferroptosis, an iron-dependent form of regulated cell death, is not related to autophagy. Conversely, recent evidence indicates that the molecular machinery of autophagy facilitates ferroptosis through the selective degradation of anti-ferroptosis regulators. However, the mechanism of autophagy-dependent ferroptosis remains incompletely understood. Here, we examine the early dynamic change in protein expression of autophagic (e.g., MAP1LC3B and SQSTM1) or ferroptotic (e.g., SLC7A11 and GPX4) regulators in 60 human cancer cell lines in response to two classical ferroptosis activators (erastin and RSL3) in the absence or presence of the lysosomal inhibitor chloroquine. Compared to erastin, RSL3 exhibits wider and stronger activity in the upregulation of MAP1LC3B-II or downregulation of SQSTM1 in 80% (48/60) or 63% (38/60) of cell lines, respectively. Both RSL3 and erastin failed to affect SLC7A11 expression, but they led to GPX4 downregulation in 12% (7/60) and 3% (2/60) of cell lines, respectively. Additionally, the intracellular iron exporter SLC40A1/ferroportin-1 was identified as a new substrate for autophagic elimination, and its degradation by SQSTM1 promoted ferroptosis

Keywords: Autophagy; cell death; ferroptosis; heterogeneity; tumor therapy

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