SSBP1 Suppresses TGFβ-Driven Epithelial-to-Mesenchymal Transition and Metastasis in Triple-Negative Breast Cancer by Regulating Mitochondrial Retrograde Signaling
Authors: Sheng Huang
Sheng Liu
Hong-Lin Jiang
Liang-Dong Li
Jiong Wu
Shui-Ping Gao
Xin Hu
He-Fen Sun
Zhi-Ming Shao
Wei Jin
Journal: Cancer Research (2016)
Discipline: CLINICAL MEDICINE
Keywords: Triple-negative breast cancer; Mitochondrial function; Metastasis; SSBP1; Tumor progression
Affiliations: Department of Breast Surgery, Key Laboratory of Breast Cancer in Shanghai, Collaborative Innovation Center of Cancer Medicine, Fudan University Shanghai Cancer Center, Shanghai, China. Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China., Department of Breast Surgery and Pharmacology Laboratory of Traditional Chinese Medicine, Long Hua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China., Department of Breast Surgery, Key Laboratory of Breast Cancer in Shanghai, Collaborative Innovation Center of Cancer Medicine, Fudan University Shanghai Cancer Center, Shanghai, China. Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China. .

Abstract:  Triple-negative breast cancer (TNBC) is a highly aggressive tumor subtype lacking effective prognostic indicators or therapeutic targets. Mitochondrial function is dysregulated frequently in cancer cells to allow for adaptation to a harsh tumor microenvironment. Targeting mitochondrial biogenesis and bioenergetics is, therefore, an attractive therapeutic strategy. In this study, we performed quantitative proteomic analyses in human parental and metastatic breast cancer cell lines to identify mitochondrial proteins involved in TNBC metastasis. We found that single-strand DNA-binding protein 1 (SSBP1) was downregulated in highly metastatic breast cancer cells. Moreover, SSBP1 downregulation promoted TNBC cell metastasis in vitro and in vivo. Mechanistically, SSBP1 loss decreased mitochondrial DNA copy number, thereby potentiating calcineurin-mediated mitochondrial retrograde signaling that induced c-Rel/p50 nuclear localization, activated TGFβ promoter activity, and TGFβ-driven epithelial-to-mesenchymal transition. Low SSBP1 expression correlated with tumor progression and poor prognosis in patients. Collectively, our findings identified SSBP1 as a novel metastasis suppressor and elucidated the mechanisms by which dysregulated mitochondrial signaling contributes to metastatic potential, providing potential new prognostic indicators for patients with TNBC. 

Retracted: No

PubPeer comments:
 In Figure 2A a western blot panel has been duplicated. ![file] , 
 Duplication of data in Figure 2A: ![file] , 
 Since there was no response to the first post, I can add some more: Figure 2D and 5D: Two cases of data duplication. Figure 5C: A western blot has been duplicated and modified (SMAD3 blot) ![file] ![file] , 
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 Hoya Camphorifolia, nice work! Is this a competition? Here is one more: Figure 2H: One mouse has been apparently rose from the dead. Last time it appeared was in Jiang HL et al., 2015 (Figure 5A; Oncotarget, PMID: 25970785). ![file] , 
 #5 All praise the Mouse Messiah. ,