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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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journal contribution
posted on 2019-02-12, 06:29 authored by Juo-Han Lin, Wen-Jui Lee, Han-Chung Wu, Chih-Hsiung Wu, Li-Ching Chen, Chi-Cheng Huang, Hang-Lung Chang, Tzu-Chun Cheng, Hui-Wen Chang, Chi-Tang Ho, Shih-Hsin Tu, Yuan-Soon Ho

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.

Funding

This work was supported by the Health and Welfare Surcharge of Tobacco Products grant [MOHW107-TDU-B-212-114014]; the TMU Research Center of Cancer Translational Medicine from The Featured Areas Research Center Program within the framework of the Higher Education Sprout Project by the Ministry of Education (MOE) in Taiwan [none]; the Ministry of Science and Technology, Taiwan [MOST105-2320-B038-053-MY3] and [MOST106-2320-B-038-046] awarded to Dr. Ho, [MOST106-2314-B-038-053-MY3] awarded to Dr. Tu, [MOST106-2320-B038-061-MY3] awarded to Dr. Chen, and [MOST104-2314-B-038-059-MY3] awarded to Dr. Wu]; and Taipei Medical University [TMU104-AE1-B12] awarded to Dr. Chen.

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