Swiprosin-1 stimulates cancer invasion and metastasis by increasing the Rho family of GTPase signaling
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Yun Hyun Huh1, Sena Oh1,2, Yu Ra Yeo1,2, In Hee Chae1,2, So Hee Kim1,2, Ji Shin Lee3, Sook Jung Yun4, Kyu Yeong Choi5, Je-Hwang Ryu6, Chang-Duk Jun2, Woo Keun Song1,2
1Bio Imaging and Cell Dynamics Research Center, Gwangju Institute of Science and Technology, Gwangju, Korea
2School of Life Sciences, Gwangju Institute of Science and Technology, Gwangju, Korea
3Department of Pathology, Chonnam National University Hwasun Hospital, Hwasun, Korea
4Department of Dermatology, Chonnam National University Hospital, Gwangju, Korea
5The Division of Natural Medical Sciences, College of Health Science, Chosun University, Gwangju, Korea
6Dental Science Research Institute and Research Center for Biomineralization Disorders, School of Dentistry, Chonnam National University, Gwangju, Korea
Woo Keun Song, e-mail: firstname.lastname@example.org
Keywords: Swiprosin-1, metastasis, invasion, migration, Rho GTPase
Received: December 04, 2014 Accepted: March 23, 2015 Published: April 11, 2015
Ectopic expression of Swiprosin-1, an actin-binding protein (also known as EF hand domain containing 2; EFHD2), enhanced motile protrusions associated with actin, such as lamellipodia and membrane ruffles. Swiprosin-1 levels were increased in various human cancer tissues, particularly at highly invasive stages of malignant melanoma. Expression of Swiprosin-1 was correlated with that of epidermal growth factor receptor (EGFR) and induced by EGF. In a mouse metastasis model, Swiprosin-1 overexpression induced pulmonary metastasis whereas its knockdown led to marked inhibition of metastasis of highly invasive melanoma cells. Swiprosin-1 at the lamellipodia and membrane ruffles controlled the direction of cell protrusion and enhanced migration velocity through activating the Rho family of small GTPases, including Rac1, Cdc42 and RhoA. Our collective findings support the potential utility of Swiprosin-1 as a therapeutic target to prevent cancer invasion and metastasis.
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