title: Bcl-3 regulates TGFβ signaling by stabilizing Smad3 during breast cancer pulmonary metastasis.
abstract: Transforming growth factor beta (TGFβ) signaling in breast cancer is selectively associated with pulmonary metastasis. However, the underlying mechanisms remain unclear. Here we show that Bcl-3, a member of the IκB family, serves as a critical regulator in TGFβ signaling to modulate breast cancer pulmonary metastasis. Bcl-3 expression was significantly associated with metastasis-free survival in breast cancer patients. Bcl-3 deletion inhibited the migration and invasion of breast cancer cells in vitro, as well as breast cancer lung metastasis in vivo. Bcl-3 was required for the expression of downstream TGFβ signaling genes that are involved in breast cancer lung metastasis. Bcl-3 knockdown enhanced the degradation of Smad3 but not Smad2 following TGFβ treatment. Bcl-3 could bind to Smad3 and prevent the ubiquitination and degradation of Smad3 protein. These results indicate that Bcl-3 serves as a promising target to prevent breast tumor lung metastasis.
authors.affiliation: The Key Laboratory of Stem Cell Biology, Institute of Health Sciences, Shanghai Jiao Tong University School of Medicine (SJTUSM) & Shanghai Institutes for Biological Sciences (SIBS), Chinese Academy of Sciences (CAS), Shanghai 200025, China.
authors.forename: Xi
authors.initials: X
authors.lastname: Chen
authors.affiliation: The Key Laboratory of Stem Cell Biology, Institute of Health Sciences, Shanghai Jiao Tong University School of Medicine (SJTUSM) & Shanghai Institutes for Biological Sciences (SIBS), Chinese Academy of Sciences (CAS), Shanghai 200025, China.
authors.forename: Xinwei
authors.initials: X
authors.lastname: Cao
authors.affiliation: The Key Laboratory of Stem Cell Biology, Institute of Health Sciences, Shanghai Jiao Tong University School of Medicine (SJTUSM) & Shanghai Institutes for Biological Sciences (SIBS), Chinese Academy of Sciences (CAS), Shanghai 200025, China.
authors.forename: Xiaohua
authors.initials: X
authors.lastname: Sun
authors.affiliation: The Key Laboratory of Stem Cell Biology, Institute of Health Sciences, Shanghai Jiao Tong University School of Medicine (SJTUSM) & Shanghai Institutes for Biological Sciences (SIBS), Chinese Academy of Sciences (CAS), Shanghai 200025, China.
authors.forename: Rong
authors.initials: R
authors.lastname: Lei
authors.affiliation: The Key Laboratory of Stem Cell Biology, Institute of Health Sciences, Shanghai Jiao Tong University School of Medicine (SJTUSM) & Shanghai Institutes for Biological Sciences (SIBS), Chinese Academy of Sciences (CAS), Shanghai 200025, China.
authors.forename: Pengfei
authors.initials: P
authors.lastname: Chen
authors.affiliation: The Key Laboratory of Stem Cell Biology, Institute of Health Sciences, Shanghai Jiao Tong University School of Medicine (SJTUSM) & Shanghai Institutes for Biological Sciences (SIBS), Chinese Academy of Sciences (CAS), Shanghai 200025, China.
authors.forename: Yongxu
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: The Key Laboratory of Stem Cell Biology, Institute of Health Sciences, Shanghai Jiao Tong University School of Medicine (SJTUSM) & Shanghai Institutes for Biological Sciences (SIBS), Chinese Academy of Sciences (CAS), Shanghai 200025, China.
authors.forename: Yuhang
authors.initials: Y
authors.lastname: Jiang
authors.affiliation: The Key Laboratory of Stem Cell Biology, Institute of Health Sciences, Shanghai Jiao Tong University School of Medicine (SJTUSM) & Shanghai Institutes for Biological Sciences (SIBS), Chinese Academy of Sciences (CAS), Shanghai 200025, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Yin
authors.affiliation: The Key Laboratory of Stem Cell Biology, Institute of Health Sciences, Shanghai Jiao Tong University School of Medicine (SJTUSM) & Shanghai Institutes for Biological Sciences (SIBS), Chinese Academy of Sciences (CAS), Shanghai 200025, China.
authors.forename: Ran
authors.initials: R
authors.lastname: Chen
authors.affiliation: The Key Laboratory of Stem Cell Biology, Institute of Health Sciences, Shanghai Jiao Tong University School of Medicine (SJTUSM) & Shanghai Institutes for Biological Sciences (SIBS), Chinese Academy of Sciences (CAS), Shanghai 200025, China.
authors.forename: Deji
authors.initials: D
authors.lastname: Ye
authors.affiliation: The Key Laboratory of Stem Cell Biology, Institute of Health Sciences, Shanghai Jiao Tong University School of Medicine (SJTUSM) & Shanghai Institutes for Biological Sciences (SIBS), Chinese Academy of Sciences (CAS), Shanghai 200025, China.
authors.forename: Qi
authors.initials: Q
authors.lastname: Wang
authors.affiliation: The Key Laboratory of Stem Cell Biology, Institute of Health Sciences, Shanghai Jiao Tong University School of Medicine (SJTUSM) & Shanghai Institutes for Biological Sciences (SIBS), Chinese Academy of Sciences (CAS), Shanghai 200025, China.
authors.forename: Zhanjie
authors.initials: Z
authors.lastname: Liu
authors.affiliation: The Key Laboratory of Stem Cell Biology, Institute of Health Sciences, Shanghai Jiao Tong University School of Medicine (SJTUSM) & Shanghai Institutes for Biological Sciences (SIBS), Chinese Academy of Sciences (CAS), Shanghai 200025, China.
authors.forename: Sanhong
authors.initials: S
authors.lastname: Liu
authors.affiliation: The Key Laboratory of Stem Cell Biology, Institute of Health Sciences, Shanghai Jiao Tong University School of Medicine (SJTUSM) & Shanghai Institutes for Biological Sciences (SIBS), Chinese Academy of Sciences (CAS), Shanghai 200025, China.
authors.forename: Chunyan
authors.initials: C
authors.lastname: Cheng
authors.affiliation: The Key Laboratory of Stem Cell Biology, Institute of Health Sciences, Shanghai Jiao Tong University School of Medicine (SJTUSM) & Shanghai Institutes for Biological Sciences (SIBS), Chinese Academy of Sciences (CAS), Shanghai 200025, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Mao
authors.affiliation: Department of Pathology, Zhongshan Hospital, Fudan University School of Medicine, Shanghai 200032, China.
authors.forename: Yingyong
authors.initials: Y
authors.lastname: Hou
authors.affiliation: Department of General Surgery, Ruijin Hospital, Shanghai Jiao-Tong University School of Medicine, Shanghai 200025, China.
authors.forename: Mingliang
authors.initials: M
authors.lastname: Wang
authors.affiliation: Laboratory of Molecular Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: Ulrich
authors.initials: U
authors.lastname: Siebenlist
authors.affiliation: The Key Laboratory of Stem Cell Biology, Institute of Health Sciences, Shanghai Jiao Tong University School of Medicine (SJTUSM) & Shanghai Institutes for Biological Sciences (SIBS), Chinese Academy of Sciences (CAS), Shanghai 200025, China.|Collaborative Innovation Center of System Biomedicine, Shanghai Jiao Tong University School of Medicine, Shanghai 200240, China.
authors.forename: Y
authors.initials: Y
authors.lastname: Eugene Chin
authors.affiliation: The Key Laboratory of Stem Cell Biology, Institute of Health Sciences, Shanghai Jiao Tong University School of Medicine (SJTUSM) & Shanghai Institutes for Biological Sciences (SIBS), Chinese Academy of Sciences (CAS), Shanghai 200025, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Liaoning Province Collaborative Innovation Center of Aging Related Disease Diagnosis and Treatment and Prevention, Shenyang 110001, China.|Key laboratory of Medical Cell Biology, China Medical University, Shenyang 110001, China.
authors.forename: Liu
authors.initials: L
authors.lastname: Cao
authors.affiliation: The Key Laboratory of Stem Cell Biology, Institute of Health Sciences, Shanghai Jiao Tong University School of Medicine (SJTUSM) & Shanghai Institutes for Biological Sciences (SIBS), Chinese Academy of Sciences (CAS), Shanghai 200025, China.|Collaborative Innovation Center of System Biomedicine, Shanghai Jiao Tong University School of Medicine, Shanghai 200240, China.
authors.forename: Guohong
authors.initials: G
authors.lastname: Hu
authors.affiliation: The Key Laboratory of Stem Cell Biology, Institute of Health Sciences, Shanghai Jiao Tong University School of Medicine (SJTUSM) & Shanghai Institutes for Biological Sciences (SIBS), Chinese Academy of Sciences (CAS), Shanghai 200025, China.|Collaborative Innovation Center of System Biomedicine, Shanghai Jiao Tong University School of Medicine, Shanghai 200240, China.
authors.forename: Xiaoren
authors.initials: X
authors.lastname: Zhang
mesh_terms: D000818:Animals; D000081242:B-Cell Lymphoma 3 Protein; D001943:Breast Neoplasms / Q000235:genetics / Q000473:pathology*; D045744:Cell Line, Tumor; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D055785:Gene Knockdown Techniques; D006801:Humans; D008175:Lung Neoplasms / Q000378:metabolism / Q000556:secondary*; D051379:Mice; D055550:Protein Stability; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D015398:Signal Transduction / Q000235:genetics; D051900:Smad3 Protein / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism*; D016212:Transforming Growth Factor beta / Q000378:metabolism*
chemical_list: D000081242:B-Cell Lymphoma 3 Protein; C000631344:BCL3 protein, human; C000631345:Bcl3 protein, mouse; D011518:Proto-Oncogene Proteins; D051900:Smad3 Protein; D014157:Transcription Factors; D016212:Transforming Growth Factor beta