Keratin 15 promotes tumor growth, invasion, epithelial-mesenchymal transition and radioresistance but represses ferroptosis via a Wnt/β-catenin signaling-related way in breast cancer.
Jiahui Jin, Peng Zhao, Chengcheng Dai, Jie Li, Ziyi Huang, Tongsong Zhang, Xuezhen Ma
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引用次数: 0
Abstract
Keratin 15 (KRT15) promotes tumor progression in several cancers, but its engagement in breast cancer is seldom uncovered. This study aimed to explore the impact of KRT15 modification on breast cancer growth, mobility, radiosensitivity, ferroptosis, and Wnt/β-catenin signaling pathway. A lentiviral vector containing short hairpin RNA or complementary DNA targeting KRT15 was transfected into MDA-MB-231 and MCF-7 cells in vitro. The transfected MCF-7 cells were further proposed to irradiation treatment. In vivo, female BALB/c nude mice were used to establish xenograft model with KRT15-overexpressed MDA-MB-231 cells and treated by irradiation. KRT15 overexpression promoted cell proliferation, migration, invasion, colony number, epithelial-mesenchymal transition (EMT, reflected by E-Cadherin, N-Cadherin, and Vimentin expressions), and S-stage cell cycle arrest in MDA-MB-231 and MCF-7 cells, but repressed cell apoptosis and ferroptosis (reflected by DMT1, SLC7A11, FTH1, and GPX4 expressions); while KRT15 knockdown exhibited the opposite effects. Importantly, KRT15 overexpression enhanced irradiation resistance in MCF-7 cells reflected by cell proliferation, migration, invasion, colony number, cell cycle, and cell apoptosis detections. Besides, KRT15 overexpression increased EMT and activated Wnt/β-catenin signaling pathway (reflected by β-catenin, TCF-1, c-Myc, CCND1, MMP7 expressions) in MCF-7 cells with or without irradiation. In vivo experiments further validated that KRT15 overexpression promoted tumor growth, EMT, Wnt/β-catenin signaling pathway, and irradiation resistance, but repressed the ferroptosis. Collectively, KRT15 may facilitate tumor growth, invasion, EMT, and radioresistance but represses ferroptosis in a Wnt/β-catenin signaling-related way, suggesting its potency as a treatment target for breast cancer management.
期刊介绍:
Molecular and Cellular Biochemistry: An International Journal for Chemical Biology in Health and Disease publishes original research papers and short communications in all areas of the biochemical sciences, emphasizing novel findings relevant to the biochemical basis of cellular function and disease processes, as well as the mechanics of action of hormones and chemical agents. Coverage includes membrane transport, receptor mechanism, immune response, secretory processes, and cytoskeletal function, as well as biochemical structure-function relationships in the cell.
In addition to the reports of original research, the journal publishes state of the art reviews. Specific subjects covered by Molecular and Cellular Biochemistry include cellular metabolism, cellular pathophysiology, enzymology, ion transport, lipid biochemistry, membrane biochemistry, molecular biology, nuclear structure and function, and protein chemistry.