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International Journal Of Bilogical Sciences

.: Home > International Journal Of Bilogical Sciences > 2013 > Volume 9 Number 1 > Xi Jiang1, 2, *, Jingyin Yue2,*, Huimei Lu2, Neil Campbell2, Qifeng Yang2,3, Shijie Lan1,2, Bruce G. Haffty2, Changji Yuan1,✉, Zhiyuan Shen2,✉

Inhibition of Filamin-A Reduces Cancer Metastatic Potential

Xi Jiang1, 2, *, Jingyin Yue2,*, Huimei Lu2, Neil Campbell2, Qifeng Yang2,3, Shijie Lan1,2, Bruce G. Haffty2, Changji Yuan1,✉, Zhiyuan Shen2,✉
1. Cancer Center, The First Hospital of Jilin University, Changchun, Jilin Province, China. 2. The Cancer Institute of New Jersey, New Brunswick, NJ 08903, USA. 3. Current address: Qilu Hospital, Shandong University, Department of Breast Surgery, Jinan, Shandong Province, China.
Abstract :

Filamin-A cross-links actin filaments into dynamic orthogonal networks, and interacts with an array of proteins of diverse cellular functions. Because several filamin-A interaction partners are implicated in signaling of cell mobility regulation, we tested the hypothesis that filamin-A plays a role in cancer metastasis. Using four pairs of filamin-A proficient and deficient isogenic cell lines, we found that filamin-A deficiency in cancer cells significantly reduces their migration and invasion. Using a xenograft tumor model with subcutaneous and intracardiac injections of tumor cells, we found that the filamin-A deficiency causes significant reduction of lung, splenic and systemic metastasis in nude mice. We evaluated the expression of filamin-A in breast cancer tissues by immunohistochemical staining, and found that low levels of filamin-A expression in cancer cells of the tumor tissues are associated with a better distant metastasis-free survival than those with normal levels of filamin-A. These data not only validate filamin-A as a prognostic marker for cancer metastasis, but also suggest that inhibition of filamin-A in cancer cells may reduce metastasis and that filamin-A can be used as a therapeutic target for filamin-A positive cancer.

Keywords :
Filamin-A, ABP-280, migration, invasiveness, metastasis, biomarker.

Date Deposited : 09 Apr 2015 15:08

Last Modified : 09 Apr 2015 15:08

Official URL: http://www.ijbs.com/ms/archive

Volume 9, Number 1, - 2013 , ISSN 1545-1003

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