Male-specific lethal 1 (MSL1) promotes Erastin-induced ferroptosis in colon cancer cells by regulating the KCTD12-SLC7A11 axis

Abstract MSL1, a scaffold protein of the MSL histone acetyltransferase complex, is crucial for its structural integrity and enzymatic activity. While MSL1 is highly expressed in various tumors, its role in tumor progression and cell death remains unclear. Here, we provide evidence of a negative regu...

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Main Authors: Lifu Luo, Qingzhi Zhao, Xueli Cui, Shijiao Dong, Yong Wang, Nan Jiang, Chengyu Cai, Jingji Jin, Bing Liang
Format: Article
Language:English
Published: Nature Publishing Group 2025-04-01
Series:Cell Death and Disease
Online Access:https://doi.org/10.1038/s41419-025-07555-7
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author Lifu Luo
Qingzhi Zhao
Xueli Cui
Shijiao Dong
Yong Wang
Nan Jiang
Chengyu Cai
Jingji Jin
Bing Liang
author_facet Lifu Luo
Qingzhi Zhao
Xueli Cui
Shijiao Dong
Yong Wang
Nan Jiang
Chengyu Cai
Jingji Jin
Bing Liang
author_sort Lifu Luo
collection DOAJ
description Abstract MSL1, a scaffold protein of the MSL histone acetyltransferase complex, is crucial for its structural integrity and enzymatic activity. While MSL1 is highly expressed in various tumors, its role in tumor progression and cell death remains unclear. Here, we provide evidence of a negative regulatory relationship between MSL1 and KCTD12 through biochemical assays and knockdown/overexpression studies. Notably, in colon cancer cells, the ferroptosis inducer Erastin significantly suppressed MSL1 expression, leading to KCTD12 upregulation. Moreover, MSL1 promotes Erastin-induced ferroptosis in HCT116 and SW480 cells via the KCTD12-SLC7A11 axis. Consistently, Erastin-induced changes in ROS, GSH, and MDA levels were regulated by this axis, highlighting its role in ferroptosis. These findings offer potential therapeutic targets and a theoretical foundation for colon cancer treatment.
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institution DOAJ
issn 2041-4889
language English
publishDate 2025-04-01
publisher Nature Publishing Group
record_format Article
series Cell Death and Disease
spelling doaj-art-d523c6ea43364d31919dca30d88b03ac2025-08-20T03:06:51ZengNature Publishing GroupCell Death and Disease2041-48892025-04-0116111210.1038/s41419-025-07555-7Male-specific lethal 1 (MSL1) promotes Erastin-induced ferroptosis in colon cancer cells by regulating the KCTD12-SLC7A11 axisLifu Luo0Qingzhi Zhao1Xueli Cui2Shijiao Dong3Yong Wang4Nan Jiang5Chengyu Cai6Jingji Jin7Bing Liang8Department of Ophthalmology, The Second Hospital of Jilin UniversitySchool of Nursing, Jilin UniversitySchool of Life Sciences, Jilin UniversitySchool of Life Sciences, Jilin UniversityUrology Department, Jilin Province People’s HospitalDepartment of Cardiovascular center, Jilin University First HospitalSchool of Life Sciences, Jilin UniversitySchool of Life Sciences, Jilin UniversitySchool of Nursing, Jilin UniversityAbstract MSL1, a scaffold protein of the MSL histone acetyltransferase complex, is crucial for its structural integrity and enzymatic activity. While MSL1 is highly expressed in various tumors, its role in tumor progression and cell death remains unclear. Here, we provide evidence of a negative regulatory relationship between MSL1 and KCTD12 through biochemical assays and knockdown/overexpression studies. Notably, in colon cancer cells, the ferroptosis inducer Erastin significantly suppressed MSL1 expression, leading to KCTD12 upregulation. Moreover, MSL1 promotes Erastin-induced ferroptosis in HCT116 and SW480 cells via the KCTD12-SLC7A11 axis. Consistently, Erastin-induced changes in ROS, GSH, and MDA levels were regulated by this axis, highlighting its role in ferroptosis. These findings offer potential therapeutic targets and a theoretical foundation for colon cancer treatment.https://doi.org/10.1038/s41419-025-07555-7
spellingShingle Lifu Luo
Qingzhi Zhao
Xueli Cui
Shijiao Dong
Yong Wang
Nan Jiang
Chengyu Cai
Jingji Jin
Bing Liang
Male-specific lethal 1 (MSL1) promotes Erastin-induced ferroptosis in colon cancer cells by regulating the KCTD12-SLC7A11 axis
Cell Death and Disease
title Male-specific lethal 1 (MSL1) promotes Erastin-induced ferroptosis in colon cancer cells by regulating the KCTD12-SLC7A11 axis
title_full Male-specific lethal 1 (MSL1) promotes Erastin-induced ferroptosis in colon cancer cells by regulating the KCTD12-SLC7A11 axis
title_fullStr Male-specific lethal 1 (MSL1) promotes Erastin-induced ferroptosis in colon cancer cells by regulating the KCTD12-SLC7A11 axis
title_full_unstemmed Male-specific lethal 1 (MSL1) promotes Erastin-induced ferroptosis in colon cancer cells by regulating the KCTD12-SLC7A11 axis
title_short Male-specific lethal 1 (MSL1) promotes Erastin-induced ferroptosis in colon cancer cells by regulating the KCTD12-SLC7A11 axis
title_sort male specific lethal 1 msl1 promotes erastin induced ferroptosis in colon cancer cells by regulating the kctd12 slc7a11 axis
url https://doi.org/10.1038/s41419-025-07555-7
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