Mitochondrial Protein UCP1 Inhibits the Malignant Behaviors of Triple-negative Breast Cancer through Activation of Mitophagy and Pyroptosis

作者全名："Xia, Jing; Chu, Changbin; Li, Wanqing; Chen, Hong; Xie, Wenhua; Cheng, Rui; Hu, Kai; Li, Xi"

作者地址："[Xia, Jing; Chu, Changbin; Li, Wanqing; Chen, Hong; Xie, Wenhua; Cheng, Rui; Li, Xi] Chongqing Med Univ, Sch Basic Med, Inst Life Sci, Chongqing 400016, Peoples R China; [Hu, Kai] Chongqing Med Univ, Key Lab Diagnost Med Designated Chinese, Minist Educ, Chongqing 400016, Peoples R China"

通信作者："Li, X (通讯作者)，Chongqing Med Univ, Sch Basic Med, Inst Life Sci, Chongqing 400016, Peoples R China."

来源：INTERNATIONAL JOURNAL OF BIOLOGICAL SCIENCES

ESI学科分类：BIOLOGY & BIOCHEMISTRY

WOS号：WOS:000790968000001

JCR分区：Q1

影响因子：9.2

年份：2022

卷号：18

期号：7

开始页：2949

结束页：2961

文献类型：Article

关键词：UCP1; Mitophagy; Pyroptosis; GSDME; Triple-negative breast cancer

摘要："Triple-negative breast cancer (TNBC) is a massive threat to women's health due to its high morbidity, malignancy, and the refractory, effective therapeutic option of TNBC is still deficient. The mitochondrial protein showed therapeutic potential on breast cancer, whereas the mechanism and downstream pathway of mitochondrial uncoupling protein 1 (UCP1) was not fully elucidated. We found that UCP1 was negatively regulated to the process of TNBC. Overexpressing UCP1 could inhibit the proliferation and metastasis of TNBC, meanwhile inducing the mitochondrial swelling and activation of mitophagy in vitro. Mitophagy activation was then assessed to elucidate whether it was downstream of UCP1 in TNBC metastasis. GSDME is the core of pyroptosis. We found that GSDME was activated in the TNBC cells when UCP1 levels were high. It regulates TNBC cell proliferation potential instead of the apoptosis process in vitro and in vivo. Our results suggested that UCP1 could inhibit the process of TNBC by activating mitophagy and pyroptosis. Impaired activation of mitophagy weakens the regulation effect of UCP1 on metastasis of TNBC, similar to the impairment of GSDME activation on the proliferation regulation of UCP1 on TNBC. UCP1 might be a novel therapeutic target of TNBC."

基金机构："Natural Science Foundation of China [81770861, 82070899, 82011530460]"

基金资助正文："This work was supported by grants from the Natural Science Foundation of China (No. 81770861, 82070899, and 82011530460). Fig 6 was created with BioRender.com."