title: Involvement of Ras GTPase-activating protein SH3 domain-binding protein 1 in the epithelial-to-mesenchymal transition-induced metastasis of breast cancer cells via the Smad signaling pathway.
abstract: In situ models of epithelial-to-mesenchymal transition (EMT)-induced carcinoma develop into metastatic carcinoma, which is associated with drug resistance and disease recurrence in human breast cancer. Ras GTPase-activating protein SH3 domain-binding protein 1 (G3BP1), an essential Ras mediator, has been implicated in cancer development, including cell growth, motility, invasion and apoptosis. Here, we demonstrated that the upregulation of G3BP1 activates the EMT in breast cancer cells. Silencing Smads almost completely blocked this G3BP1-induced EMT, suggesting that this process depends on the Smad signaling pathway. We also found that G3BP1 interacted with the Smad complex. Based on these results, we proposed that G3BP1 might act as a novel co-factor of Smads by regulating their phosphorylation status. Moreover, knockdown of G3BP1 suppressed the mesenchymal phenotype of MDA-MB-231 cells in vitro and suppressed tumor growth and lung metastasis of 4T1 cells in vivo. Our findings identified a novel function of G3BP1 in the progression of breast cancer via activation of the EMT, indicating that G3BP1 might represent a potential therapeutic target for metastatic human breast cancer.
authors.affiliation: Department of Oncology, Institute of Medicinal Biotechnology, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, China.
authors.forename: Hao
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Department of Oncology, Institute of Medicinal Biotechnology, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Ma
authors.affiliation: Department of Oncology, Institute of Medicinal Biotechnology, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, China.
authors.forename: Shenghua
authors.initials: S
authors.lastname: Zhang
authors.affiliation: Department of Oncology, Institute of Medicinal Biotechnology, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, China.
authors.forename: Hong
authors.initials: H
authors.lastname: Liu
authors.affiliation: Department of Oncology, Institute of Medicinal Biotechnology, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, China.
authors.forename: Hongwei
authors.initials: H
authors.lastname: He
authors.affiliation: Department of Oncology, Institute of Medicinal Biotechnology, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, China.
authors.forename: Naren
authors.initials: N
authors.lastname: Li
authors.affiliation: Department of Oncology, Institute of Medicinal Biotechnology, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, China.
authors.forename: Yuyan
authors.initials: Y
authors.lastname: Gong
authors.affiliation: Department of Oncology, Institute of Medicinal Biotechnology, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, China.
authors.forename: Shuangshuang
authors.initials: S
authors.lastname: Zhao
authors.affiliation: Institute of Medicinal Biotechnology, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, China.|State Key Laboratory of Bioactive Substances and Functions of Natural Medicines, Institute of Materia Medica, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, China.
authors.forename: Jian-Dong
authors.initials: JD
authors.lastname: Jiang
authors.affiliation: Department of Oncology, Institute of Medicinal Biotechnology, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, China.
authors.forename: Rong-Guang
authors.initials: RG
authors.lastname: Shao
mesh_terms: D000818:Animals; D015153:Blotting, Western; D001943:Breast Neoplasms / Q000473:pathology*; D002352:Carrier Proteins / Q000378:metabolism*; D045744:Cell Line, Tumor; D004265:DNA Helicases; D058750:Epithelial-Mesenchymal Transition / Q000502:physiology*; D005260:Female; D005455:Fluorescent Antibody Technique; D055785:Gene Knockdown Techniques; D006801:Humans; D047468:Immunoprecipitation; D008807:Mice, Inbred BALB C; D009361:Neoplasm Invasiveness / Q000473:pathology; D000075223:Poly-ADP-Ribose Binding Proteins; D020365:RNA Helicases; D000067776:RNA Recognition Motif Proteins; D034741:RNA, Small Interfering; D015398:Signal Transduction / Q000502:physiology*; D051785:Smad Proteins / Q000378:metabolism*; D014162:Transfection
chemical_list: D002352:Carrier Proteins; D000075223:Poly-ADP-Ribose Binding Proteins; D000067776:RNA Recognition Motif Proteins; D034741:RNA, Small Interfering; D051785:Smad Proteins; D004265:DNA Helicases; C116070:G3BP1 protein, human; C492055:G3bp1 protein, mouse; D020365:RNA Helicases
keywords: EMT; G3BP1; Smad signaling pathway; breast cancer