Small G protein signalling modulator 2 (SGSM2) is involved in oestrogen receptor-positive breast cancer metastasis through enhancement of migratory cell adhesion via interaction with E-cadherin |
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| Authors: | Juo-Han Lin Wen-Jui Lee Han-Chung Wu Chih-Hsiung Wu Li-Ching Chen Chi-Cheng Huang |
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| Institution: | 1. Ph.D. Program for Cancer Molecular Biology and Drug Discovery, College of Medical Science and Technology, Taipei Medical University and Academia Sinica, Taipei, Taiwan;2. Ph.D. Program for Neural Regenerative Medicine, College of Medical Science and Technology, Taipei Medical University and National Health Research Institutes, Taipei, Taiwan;3. Institute of Cellular and Organismic Biology, Academia Sinica, Taipei, Taiwan;4. Department of Surgery, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan;5. Department of General Surgery, En Chu Kong Hospital, New Taipei City, Taiwan;6. Breast Medical Center, Taipei Medical University Hospital, Taipei, Taiwan;7. Taipei Cancer Center, Taipei Medical University, Taipei, Taiwan;8. TMU Research Center of Cancer Translational Medicine, Taipei Medical University, Taipei, Taiwan;9. School of Medicine, College of Medicine, Fu-Jen Catholic University, New Taipei City, Taiwan;10. Department of Surgery, Fu-Jen Catholic University Hospital, New Taipei City, Taiwan |
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| Abstract: | The function of small G protein signalling modulators (SGSM1/2/3) in cancer remains unknown. Our findings demonstrated that SGSM2 is a plasma membrane protein that strongly interacted with E-cadherin/β-catenin. SGSM2 downregulation enhanced the phosphorylation of focal adhesion kinase (FAK; Y576/577), decreased the expression of epithelial markers such as E-cadherin, β-catenin, and Paxillin, and increased the expression of Snail and Twist-1, which reduced cell adhesion and promoted cancer cell migration. Oestrogen and fibronectin treatment was found to promote the colocalization of SGSM2 at the leading edge with phospho-FAK (Y397). The BioGRID database showed that SGSM2 potentially interacts with cytoskeleton remodelling and cell-cell junction proteins. These evidences suggest that SGSM2 plays a role in modulating cell adhesion and cytoskeleton dynamics during cancer migration. |
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| Keywords: | SGSM breast cancer cell adhesion E-cadherin oestrogen receptor EMT |
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