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SHF confers radioresistance in colorectal cancer by the regulation of mitochondrial DNA copy number

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机构： [1]Gastrointestinal Surgery Ward II, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, China [2] Thoracic Surgery Ward II, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, China [3] Gastrointestinal Surgery Ward I, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, China [4]Sichuan Cancer Hospital and Institute, Sichuan Cancer Center, School of Medicine, University of Electronic Science and Technology of China, Chengdu, China [5] Radiation Oncology Key Laboratory of Sichuan Province, Chengdu, China

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关键词： Colorectal cancer Mitochondrial function Radiosensitivity Radioresistance Mitochondrial DNA copy number

摘要：

Altered mitochondrial function contributes greatly to pathogenesis and progression of colorectal cancer. In this study, we report a functional pool of Src homology 2 domain-containing F (SHF) in mitochondria controlling the response of colorectal cancer cells to radiation therapy. We found that elevated expression of SHF in cancer cells is essential for promoting mitochondrial function by increasing mitochondrial DNA copy number, thus reducing the sensitivity of colorectal cancer cells to radiation. Mechanistically, SHF binds to mitochondrial DNA and promotes POLG/SSBP1-mediated mitochondrial DNA synthesis. Importantly, SHF loss-mediated radiosensitization was phenocopied by depletion of mitochondrial DNA. Thus, our data demonstrate that mitochondrial SHF is an important regulator of radioresistance in colorectal cancer cells, identifying SHF as a promising therapeutic target to enhance radiotherapy efficacy in colorectal cancer.© 2022. The Author(s), under exclusive licence to Springer Nature Switzerland AG.

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出版当年[2023]版：

大类 | 4 区医学

小类 | 4 区医学：研究与实验

最新[2023]版：

大类 | 4 区医学

小类 | 4 区医学：研究与实验

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出版当年[2023]版：

Q2 MEDICINE, RESEARCH & EXPERIMENTAL

最新[2023]版：

Q2 MEDICINE, RESEARCH & EXPERIMENTAL

影响因子： 3.2 最新[2023版] 3.4 最新五年平均 3.2 出版当年[2023版] 3.4 出版当年五年平均 4.6 出版前一年[2022版]

第一作者：

第一作者机构： [1]Gastrointestinal Surgery Ward II, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, China

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通讯作者：

通讯机构： [4]Sichuan Cancer Hospital and Institute, Sichuan Cancer Center, School of Medicine, University of Electronic Science and Technology of China, Chengdu, China [5] Radiation Oncology Key Laboratory of Sichuan Province, Chengdu, China

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SHF confers radioresistance in colorectal cancer by the regulation of mitochondrial DNA copy number

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