DAB2IP inhibits glucose uptake by modulating HIF-1α ubiquitination under hypoxia in breast cancer

作者全名：Dong, Hongliang; Jia, Weiyi; Meng, Weijian; Zhang, Rui; Qi, Zhihong; Chen, Zhuo; Xie, Sophia; Min, Jiang; Liu, Liang; Shen, Jie

作者地址：[Dong, Hongliang; Jia, Weiyi; Meng, Weijian; Zhang, Rui; Qi, Zhihong; Chen, Zhuo; Liu, Liang; Shen, Jie] Huazhong Univ Sci & Technol, Tongji Hosp, Tongji Med Coll, Dept GI Surg, Wuhan 430030, Peoples R China; [Dong, Hongliang; Jia, Weiyi; Meng, Weijian; Zhang, Rui; Qi, Zhihong; Chen, Zhuo; Liu, Liang; Shen, Jie] Huazhong Univ Sci & Technol, Tongji Hosp, GI Canc Res Inst, Tongji Med Coll, Wuhan 430030, Peoples R China; [Jia, Weiyi] Zhengzhou Univ, Zhengzhou Cent Hosp, Dept Sci & Educ, Zhengzhou 450007, Peoples R China; [Xie, Sophia] Wuhan Britain China Sch, Wuhan 430030, Peoples R China; [Min, Jiang] Chongqing Med Univ, Affiliated Hosp 1, Gastrointestinal Surg Dept, Chongqing 40000, Peoples R China

通信作者：Liu, L; Shen, J (通讯作者)，Huazhong Univ Sci & Technol, Tongji Hosp, Tongji Med Coll, Dept GI Surg, Wuhan 430030, Peoples R China.; Liu, L; Shen, J (通讯作者)，Huazhong Univ Sci & Technol, Tongji Hosp, GI Canc Res Inst, Tongji Med Coll, Wuhan 430030, Peoples R China.

来源：ONCOGENESIS

ESI学科分类：BIOLOGY & BIOCHEMISTRY

WOS号：WOS:001243983600001

JCR分区：Q1

影响因子：5.9

年份：2024

卷号：13

期号：1

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结束页：　

文献类型：Article

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摘要：Metabolic reprogramming has become increasingly important in tumor biology research. The glucose metabolic pathway is a major energy source and is often dysregulated in breast cancer. DAB2IP is widely reported to be a tumor suppressor that acts as a scaffold protein to suppress tumor malignancy in breast cancer. Interestingly, DAB2IP has also been found to be a potential regulator of glucose uptake; however, the exact mechanism remains unclear. In this study, we found that DAB2IP inhibited glucose uptake under hypoxia conditions in breast cancer cells by suppressing HIF-1 alpha signals. Mechanically, DAB2IP interacted with the E3 ubiquitin ligase STUB1 via its PER domain, thus triggering STUB1 mediated HIF-1 alpha ubiquitylation and degradation, and inhibit glucose metabolism and tumor progression. Deleting the PER domain abrogated the DAB2IP-related inhibitory effects on glucose uptake, intracellular ATP production, and lactic acid production in breast cancer cells. These findings elucidate the biological roles of DAB2IP in cancer-related glucose metabolism as well as a novel mechanism by which STUB1-driven HIF-1 alpha ubiquitylated degradation is regulated in breast cancer.

基金机构：Natural Science Foundation of Hubei Province (Hubei Provincial Natural Science Foundation)

基金资助正文：We thank the Experimental Medicine Center of Tongji Hospital for providing support for our experiments. We thank the Department of Pathology of Tongji Hospital for providing assistance with pathological analysis. We also thank the Department of Radiology of Tongji Hospital for providing assistance with the PET/CT scan analysis, and the Nuclear Medicine Department of Wuhan Union Hospital for providing assistance with the small animal micro-PET/CT scan. We would like to thank Editage (www.editage.cn) for English language editing.