Blocking SLC7A11 attenuates the proliferation of esophageal squamous cell carcinoma cells

The role of ferroptosis-associated gene SLC7A11 in esophageal cancer progression is largely unknown, therefore, the effects of blocking SLC7A11 on esophageal squamous cell carcinoma (ESCC) cells are evaluated. Results showed that SLC7A11 was overexpressed in ESCC tissues both in mRNA and protein lev...

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Main Authors: Wen-Ting Li, Xin Jin, Sheng-Jie Song, Chong Wang, Chuang Fu, Wen Jiang, Jie Bai, Zhi-Zhou Shi
Format: Article
Language:English
Published: Taylor & Francis Group 2024-12-01
Series:Animal Cells and Systems
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Online Access:https://www.tandfonline.com/doi/10.1080/19768354.2024.2346981
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author Wen-Ting Li
Xin Jin
Sheng-Jie Song
Chong Wang
Chuang Fu
Wen Jiang
Jie Bai
Zhi-Zhou Shi
author_facet Wen-Ting Li
Xin Jin
Sheng-Jie Song
Chong Wang
Chuang Fu
Wen Jiang
Jie Bai
Zhi-Zhou Shi
author_sort Wen-Ting Li
collection DOAJ
description The role of ferroptosis-associated gene SLC7A11 in esophageal cancer progression is largely unknown, therefore, the effects of blocking SLC7A11 on esophageal squamous cell carcinoma (ESCC) cells are evaluated. Results showed that SLC7A11 was overexpressed in ESCC tissues both in mRNA and protein levels. Blocking SLC7A11 using Erastin suppressed the proliferation and colony formation of ESCC cells, decreased cellular ATP levels, and improved ROS production. Sixty-three SLC7A11-binding proteins were identified using the IP-MS method, and these proteins were enriched in four signaling pathways, including spliceosome, ribosome, huntington disease, and diabetic cardiomyopathy. The deubiquitinase inhibitors PR-619, GRL0617, and P 22077 could reduce at least 40% protein expression level of SLC7A11 in ESCC cells, and PR-619 and GRL0617 exhibited suppressive effects on the cell viability and colony formation ability of KYSE30 cells, respectively. Erastin downregulated GPX4 and DHODH and also reduced the levels of β-catenin, p-STAT3, and IL-6 in ESCC cells. In conclusion, SLC7A11 was overexpressed in ESCC, and blocking SLC7A11 using Erastin mitigated malignant phenotypes of ESCC cells and downregulated key ferroptosis-associated molecules GPX4 and DHODH. The therapeutic potential of targeting SLC7A11 should be further evaluated in the future.
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spelling doaj-art-64dd97c009fd4ca3a3ff37d2838c93b52025-08-20T03:06:14ZengTaylor & Francis GroupAnimal Cells and Systems1976-83542151-24852024-12-0128123725010.1080/19768354.2024.2346981Blocking SLC7A11 attenuates the proliferation of esophageal squamous cell carcinoma cellsWen-Ting Li0Xin Jin1Sheng-Jie Song2Chong Wang3Chuang Fu4Wen Jiang5Jie Bai6Zhi-Zhou Shi7Medical School, Kunming University of Science and Technology, Kunming, People’s Republic of ChinaMedical School, Kunming University of Science and Technology, Kunming, People’s Republic of ChinaMedical School, Kunming University of Science and Technology, Kunming, People’s Republic of ChinaMedical School, Kunming University of Science and Technology, Kunming, People’s Republic of ChinaMedical School, Kunming University of Science and Technology, Kunming, People’s Republic of ChinaDepartment of Thoracic Surgery, The First People's Hospital of Yunnan Province & The Affiliated Hospital of Kunming University of Science and Technology, Kunming, People’s Republic of ChinaMedical School, Kunming University of Science and Technology, Kunming, People’s Republic of ChinaMedical School, Kunming University of Science and Technology, Kunming, People’s Republic of ChinaThe role of ferroptosis-associated gene SLC7A11 in esophageal cancer progression is largely unknown, therefore, the effects of blocking SLC7A11 on esophageal squamous cell carcinoma (ESCC) cells are evaluated. Results showed that SLC7A11 was overexpressed in ESCC tissues both in mRNA and protein levels. Blocking SLC7A11 using Erastin suppressed the proliferation and colony formation of ESCC cells, decreased cellular ATP levels, and improved ROS production. Sixty-three SLC7A11-binding proteins were identified using the IP-MS method, and these proteins were enriched in four signaling pathways, including spliceosome, ribosome, huntington disease, and diabetic cardiomyopathy. The deubiquitinase inhibitors PR-619, GRL0617, and P 22077 could reduce at least 40% protein expression level of SLC7A11 in ESCC cells, and PR-619 and GRL0617 exhibited suppressive effects on the cell viability and colony formation ability of KYSE30 cells, respectively. Erastin downregulated GPX4 and DHODH and also reduced the levels of β-catenin, p-STAT3, and IL-6 in ESCC cells. In conclusion, SLC7A11 was overexpressed in ESCC, and blocking SLC7A11 using Erastin mitigated malignant phenotypes of ESCC cells and downregulated key ferroptosis-associated molecules GPX4 and DHODH. The therapeutic potential of targeting SLC7A11 should be further evaluated in the future.https://www.tandfonline.com/doi/10.1080/19768354.2024.2346981SLC7A11ErastinESCCGPX4
spellingShingle Wen-Ting Li
Xin Jin
Sheng-Jie Song
Chong Wang
Chuang Fu
Wen Jiang
Jie Bai
Zhi-Zhou Shi
Blocking SLC7A11 attenuates the proliferation of esophageal squamous cell carcinoma cells
Animal Cells and Systems
SLC7A11
Erastin
ESCC
GPX4
title Blocking SLC7A11 attenuates the proliferation of esophageal squamous cell carcinoma cells
title_full Blocking SLC7A11 attenuates the proliferation of esophageal squamous cell carcinoma cells
title_fullStr Blocking SLC7A11 attenuates the proliferation of esophageal squamous cell carcinoma cells
title_full_unstemmed Blocking SLC7A11 attenuates the proliferation of esophageal squamous cell carcinoma cells
title_short Blocking SLC7A11 attenuates the proliferation of esophageal squamous cell carcinoma cells
title_sort blocking slc7a11 attenuates the proliferation of esophageal squamous cell carcinoma cells
topic SLC7A11
Erastin
ESCC
GPX4
url https://www.tandfonline.com/doi/10.1080/19768354.2024.2346981
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