title: Inhibition of filamin-A reduces cancer metastatic potential.
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.
authors.affiliation: Cancer Center, The First Hospital of Jilin University, Changchun, Jilin Province, China.
authors.forename: Xi
authors.initials: X
authors.lastname: Jiang
authors.forename: Jingyin
authors.initials: J
authors.lastname: Yue
authors.forename: Huimei
authors.initials: H
authors.lastname: Lu
authors.forename: Neil
authors.initials: N
authors.lastname: Campbell
authors.forename: Qifeng
authors.initials: Q
authors.lastname: Yang
authors.forename: Shijie
authors.initials: S
authors.lastname: Lan
authors.forename: Bruce G
authors.initials: BG
authors.lastname: Haffty
authors.forename: Changji
authors.initials: C
authors.lastname: Yuan
authors.forename: Zhiyuan
authors.initials: Z
authors.lastname: Shen
mesh_terms: D000818:Animals; D001943:Breast Neoplasms / Q000150:complications* / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D003285:Contractile Proteins / Q000235:genetics / Q000378:metabolism*; D005260:Female; D064448:Filamins; D015972:Gene Expression Regulation, Neoplastic; D007150:Immunohistochemistry; D008175:Lung Neoplasms / Q000235:genetics / Q000378:metabolism / Q000556:secondary; D051379:Mice; D008840:Microfilament Proteins / Q000235:genetics / Q000378:metabolism*; D009362:Neoplasm Metastasis / Q000235:genetics
chemical_list: D003285:Contractile Proteins; D064448:Filamins; D008840:Microfilament Proteins
keywords: ABP-280; Filamin-A; biomarker.; invasiveness; metastasis; migration