Inhibition of filamin-A reduces cancer metastatic potential

Int J Biol Sci. 2013;9(1):67-77. doi: 10.7150/ijbs.5577. Epub 2012 Dec 21.


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: ABP-280; Filamin-A; biomarker.; invasiveness; metastasis; migration.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Breast Neoplasms / complications*
  • Breast Neoplasms / genetics
  • Breast Neoplasms / metabolism*
  • Cell Line, Tumor
  • Contractile Proteins / genetics
  • Contractile Proteins / metabolism*
  • Female
  • Filamins
  • Gene Expression Regulation, Neoplastic
  • Immunohistochemistry
  • Lung Neoplasms / genetics
  • Lung Neoplasms / metabolism
  • Lung Neoplasms / secondary
  • Mice
  • Microfilament Proteins / genetics
  • Microfilament Proteins / metabolism*
  • Neoplasm Metastasis / genetics


  • Contractile Proteins
  • Filamins
  • Microfilament Proteins