Nuclear SIPA1 activates integrin β1 promoter and promotes invasion of breast cancer cells.
SIPA1 (signal-induced proliferation-associated protein 1) is a GTPase activation protein that can catalyze the hydrolysis of Rap1 bound GTP to GDP. Recently attention has been paid to a potential role for SIPA1 in cancer metastasis; however, the underlying mechanism of how changes in SIPA1 levels may lead to increased metastasis remains poorly understood. In this study, we showed that SIPA1 was mainly localized to the nuclei in highly invasive breast cancer tumor tissue and MDA-MB-231 cells. Knockdown of SIPA1 in MDA-MB-231 altered cell morphology and cell proliferation ability. Furthermore, this study is the first to establish that nuclear SIPA1 can interact with the integrin β1 promoter and activate its transcription; this interaction appears to be important for SIPA1-dependent MDA-MB-231 cell adhesion and invasion. We also demonstrated that the phosphorylation of FAK, Akt and the expression of MMP9, downstream signaling molecules of integrin β1, were decreased upon SIPA1 knockdown, and MDA-MB-231 cell invasion was impaired. Taken together, these results suggest nuclear SIPA1 contributes to breast cancer cell invasion through the regulation of integrin β1 signaling.
Key Laboratory of Molecular Biophysics of Ministry of Education, School of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, China.
Y
Y
Zhang
Department of Breast Surgery, Hubei Cancer Hospital, Wuhan, China.
Y
Y
Gong
Key Laboratory of Molecular Biophysics of Ministry of Education, School of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, China.
D
D
Hu
Key Laboratory of Molecular Biophysics of Ministry of Education, School of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, China.
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P
Zhu
Key Laboratory of Molecular Biophysics of Ministry of Education, School of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, China.
N
N
Wang
Key Laboratory of Molecular Biophysics of Ministry of Education, School of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, China.
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Q
Zhang
Department of Pathology, Hubei Cancer Hospital, Wuhan, China.
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M
Wang
Key Laboratory of Molecular Biophysics of Ministry of Education, School of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, China.
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A
Aldeewan
Department of Pathology, Hubei Cancer Hospital, Wuhan, China.
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H
Xia
Department of Thyroid and Breast Surgery, Union Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
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X
Qu
Institute for Genomic and Personalized Medicine, School of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, China.
B Z
BZ
Ring
Department of Immunology and Cell Biology, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
N
N
Minato
Key Laboratory of Molecular Biophysics of Ministry of Education, School of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, China.
L
L
Su
D000818:Animals; D030801:Animals, Genetically Modified; D001943:Breast Neoplasms / Q000473:pathology*; D002448:Cell Adhesion / Q000502:physiology; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics / Q000502:physiology; D002467:Cell Nucleus / Q000378:metabolism; D049109:Cell Proliferation / Q000235:genetics / Q000502:physiology; D005260:Female; D051417:Focal Adhesion Kinase 1 / Q000378:metabolism; D020690:GTPase-Activating Proteins / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D019012:Integrin beta1 / Q000235:genetics / Q000378:metabolism*; D061986:MCF-7 Cells; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D009361:Neoplasm Invasiveness / Q000235:genetics; D009687:Nuclear Proteins / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D034622:RNA Interference; D034741:RNA, Small Interfering; D015398:Signal Transduction; D015027:Zebrafish
D020690:GTPase-Activating Proteins; D019012:Integrin beta1; D009687:Nuclear Proteins; D034741:RNA, Small Interfering; C490403:SIPA1 protein, human; D051417:Focal Adhesion Kinase 1; C496050:PTK2 protein, human; D051057:Proto-Oncogene Proteins c-akt; C579270:MMP9 protein, human; D020780:Matrix Metalloproteinase 9