角蛋白15在乳腺癌中促进肿瘤生长、侵袭、上皮-间质转化和放射耐药,但通过Wnt/β-catenin信号相关方式抑制铁下垂。

IF 3.7 2区 生物学 Q3 CELL BIOLOGY
Jiahui Jin, Peng Zhao, Chengcheng Dai, Jie Li, Ziyi Huang, Tongsong Zhang, Xuezhen Ma
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引用次数: 0

摘要

角蛋白15 (KRT15)在几种癌症中促进肿瘤进展,但其在乳腺癌中的作用很少被发现。本研究旨在探讨KRT15修饰对乳腺癌生长、迁移、放射敏感性、铁下垂和Wnt/β-catenin信号通路的影响。将含有短发夹RNA或靶向KRT15的互补DNA的慢病毒载体转染MDA-MB-231和MCF-7细胞。转染后的MCF-7细胞进一步接受辐照处理。在体内,用雌性BALB/c裸鼠与krt15过表达的MDA-MB-231细胞建立异种移植模型,并进行辐照处理。KRT15过表达促进MDA-MB-231和MCF-7细胞的细胞增殖、迁移、侵袭、集落数量、上皮-间质转化(EMT,通过E-Cadherin、N-Cadherin和Vimentin表达反映)和s期细胞周期阻滞,但抑制细胞凋亡和铁凋亡(通过DMT1、SLC7A11、FTH1和GPX4表达反映);而KRT15敲低则表现出相反的效果。重要的是,KRT15过表达增强了MCF-7细胞的辐照抗性,这反映在细胞增殖、迁移、侵袭、集落数量、细胞周期和细胞凋亡检测中。此外,KRT15过表达增加了MCF-7细胞的EMT,激活了Wnt/β-catenin信号通路(通过β-catenin、TCF-1、c-Myc、CCND1、MMP7表达)。体内实验进一步验证了KRT15过表达促进肿瘤生长、EMT、Wnt/β-catenin信号通路和辐照抗性,但抑制铁下垂。总的来说,KRT15可能促进肿瘤生长、侵袭、EMT和放射耐药,但以Wnt/β-catenin信号传导相关的方式抑制铁下垂,表明其作为乳腺癌治疗靶点的潜力。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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.

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.

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来源期刊
Molecular and Cellular Biochemistry
Molecular and Cellular Biochemistry 生物-细胞生物学
CiteScore
8.30
自引率
2.30%
发文量
293
审稿时长
1.7 months
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.
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