Slingshot-1L, a cofilin phosphatase, induces primary breast cancer metastasis
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Chen Chen1,*, Yusufu Maimaiti2,*, Shen Zhijun3, Liu Zeming1, Guo Yawen1, Yu Pan1 and Huang Tao1
1Department of Breast and Thyroid Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, P.R. China
2Department of General Surgery (Research Institute of Minimally Invasive), People’s Hospital of Xinjiang Uygur Autonomous Region, Urumqi 830000, P.R. China
3Clinical Laboratory, The Third People’s Hospital of Hubei Province, Wuhan 430000, P.R. China
*These authors have contributed equally to this work
Huang Tao, email: [email protected]
Keywords: breast cancer, cofilin, slingshot, membrane protrusionm, actin dynamics
Received: May 10, 2017 Accepted: June 28, 2017 Published: August 03, 2017
Slingshot (SSH) is a member of the conserved family of cofilin phosphatases that plays a critical role in cell membrane protrusion and migration by transforming inactive phosphorylated cofilin to an active form. SSH-like protein 1 (SSH-1L) expression is detected in various types of tumors; insulin induces the phosphatases activity of SSH-1L in a phosphoinositide 3-kinase-dependent manner. However, little is known about the expression and role of SSH-1L in breast cancer. Here, we analyzed 295 human breast cancer tissue specimens for SSH-1L expression by immunohistochemistry. The correlation between SSH-1L level and patients’ clinical characteristics was analyzed with Pearson’s χ2 test. The function of SSH-1L was evaluated by gene knockdown and quantitative real-time polymerase chain reaction detection of cofilin expression in MDA-MB-231, MCF-7, and SK-BR-3 human breast cancer cell lines. SSH-1L expression was detected in 88.1% of tissue specimens by immunohistochemistry and was strongly associated with increased metastasis and mortality. Loss of SSH-1L expression decreased the nonphosphorylated, active form of cofilin in SK-BR-3 and MDA-MB-231 cell lines, which was associated with reduced cell motility. Accordingly, SSH-1L/cofilin signaling played a critical role in primary breast cancer metastasis and was a potential therapeutic target for breast cancer treatment.
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