GDF15 knockdown promotes erastin-induced ferroptosis by decreasing SLC7A11 expression

Liang Chen; Linlin Qiao; Yue Bian; Xiuju Sun

doi:10.1016/j.bbrc.2020.03.079

GDF15 knockdown promotes erastin-induced ferroptosis by decreasing SLC7A11 expression

Biochem Biophys Res Commun. 2020 May 28;526(2):293-299. doi: 10.1016/j.bbrc.2020.03.079. Epub 2020 Mar 21.

Authors

Liang Chen¹, Linlin Qiao², Yue Bian³, Xiuju Sun⁴

Affiliations

¹ Department of Medical Genetics, China Medical University, Shenyang, 110122, Liaoning, China. Electronic address: lchen87@cmu.edu.cn.
² Department of Medical Genetics, China Medical University, Shenyang, 110122, Liaoning, China. Electronic address: llqiao@cmu.edu.cn.
³ Department of Medical Genetics, China Medical University, Shenyang, 110122, Liaoning, China; Department of Obstetrics and Gynecology, Shengjing Hospital, China Medical University, Shenyang, 110004, Liaoning, China. Electronic address: bianyue@cum.edu.cn.
⁴ Department of Medical Genetics, China Medical University, Shenyang, 110122, Liaoning, China. Electronic address: xjsun@cmu.edu.cn.

PMID: 32209255
DOI: 10.1016/j.bbrc.2020.03.079

Abstract

Ferroptosis is an iron-dependent form of regulated cell death. GDF15 affects various properties of cancer cells, but the role of GDF15 in ferroptosis has not been reported. In the present study, we found that GDF15 knockdown led to decreased expression of SLC7A11, which is a key component of system X_c^- and a regulator of ferroptosis, indicating that GDF15 might play important roles in ferroptosis. CCK8 assay showed that GDF15 knockdown promoted erastin-induced ferroptosis in MGC803 cells. qRT-PCR and western blotting results demonstrated that GDF15 inhibition attenuated the increased SLC7A11 expression induced by erastin. Further study revealed that GDF15 knockdown promoted the decreased level of extracellular glutamate and intracellular GSH as well as the increased level of lipid ROS in the presence of erastin in MGC803 cells. Overall, the study shows that GDF15 knockdown promotes erastin-induced ferroptosis in MGC803 cells by attenuating the expression of SLC7A11 and the function of system X_c^-.

Keywords: Erastin; Ferroptosis; GDF15; Gastric cancer cells; SLC7A11.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Amino Acid Transport System y+ / genetics*
Antineoplastic Agents / pharmacology*
Cell Line, Tumor
Ferroptosis / drug effects*
Gene Expression Regulation, Neoplastic / drug effects
Gene Knockdown Techniques
Growth Differentiation Factor 15 / genetics*
Humans
Piperazines / pharmacology*
Stomach Neoplasms / drug therapy*
Stomach Neoplasms / genetics

Substances

Amino Acid Transport System y+
Antineoplastic Agents
GDF15 protein, human
Growth Differentiation Factor 15
Piperazines
SLC7A11 protein, human
erastin