Int J Biol Sci 2013; 9(1):67-77. doi:10.7150/ijbs.5577
Inhibition of Filamin-A Reduces Cancer Metastatic Potential
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.
* Authors with equal contribution.
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.
Jiang X, Yue J, Lu H, Campbell N, Yang Q, Lan S, Haffty BG, Yuan C, Shen Z. Inhibition of Filamin-A Reduces Cancer Metastatic Potential. Int J Biol Sci 2013; 9(1):67-77. doi:10.7150/ijbs.5577. Available from http://www.ijbs.com/v09p0067.htm