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Targeting FAM134B-mediated reticulophagy activates sorafenib-induced ferroptosis in hepatocellular carcinoma.
- Source :
-
Biochemical and biophysical research communications [Biochem Biophys Res Commun] 2022 Jan 22; Vol. 589, pp. 247-253. Date of Electronic Publication: 2021 Dec 10. - Publication Year :
- 2022
-
Abstract
- Ferroptosis is a kind of cell death closely related to selective autophagy, such as ferritinophagy, lipophagy, clockophagy and chaperone-mediated autophagy. However, the role of reticulophagy, which specifically degrades endoplasmic reticulum (ER) fragments (also known as ER-phagy), in ferroptosis regulation is still unclear. In this study, we found that sorafenib (ferroptosis inducer) can effectively activate the receptor protein FAM134B-mediated ER-phagy, and FAM134B knockdown not only blocked ER-phagy but also significantly strengthened cellular sensitivity to ferroptosis without affecting macroautophagy. In vivo experiments also yielded similar results. These evidences provided new clues for ferroptosis regulation. Subsequently, bioinformatic analysis combined with RNA binding protein immunoprecipitation and polyribosome fractionation preliminarily indicated that PABPC1 can interact with FAM134B mRNA and promote its translation. Taken together, this study revealed the role of the PABPC1-FAM134B-ER-phagy pathway on ferroptosis, providing important evidence for novel anti-cancer strategies.<br />Competing Interests: Declaration of competing interest There are no conflicts of interest to declare.<br /> (Copyright © 2021 Elsevier Inc. All rights reserved.)
- Subjects :
- Animals
Carcinoma, Hepatocellular pathology
Cell Line, Tumor
Down-Regulation drug effects
Endoplasmic Reticulum metabolism
Endoplasmic Reticulum ultrastructure
Humans
Liver Neoplasms pathology
Male
Mice, Inbred BALB C
Mice, Nude
Poly(A)-Binding Protein I metabolism
Protein Biosynthesis drug effects
Mice
Autophagy drug effects
Carcinoma, Hepatocellular metabolism
Ferroptosis drug effects
Intracellular Signaling Peptides and Proteins metabolism
Liver Neoplasms metabolism
Membrane Proteins metabolism
Sorafenib pharmacology
Subjects
Details
- Language :
- English
- ISSN :
- 1090-2104
- Volume :
- 589
- Database :
- MEDLINE
- Journal :
- Biochemical and biophysical research communications
- Publication Type :
- Academic Journal
- Accession number :
- 34929448
- Full Text :
- https://doi.org/10.1016/j.bbrc.2021.12.019