Filamin A: Insights into its Exact Role in Cancers
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Filamin A (FlnA) is a well-known actin cross-linking protein. It serves as a scaffold for over 90 binding partners and involves in multiple cell functions, of which cell migration and adhesion is especially critical. Recently, its role in the cell has come under scrutiny for FlnA’s involvement in cancer development. Originally revealed as a cancer-promoting protein, FlnA actually plays a dual role in cancers. When localized to the cytoplasm, FlnA has a tumor-promoting effect by interacting with signaling molecules. While once localized to the nucleus, it may act to suppress tumor growth and inhibit metastasis by interacting with transcription factors. Thus drugs that can cause FlnA to transpose from cytoplasm to nucleus could be a promising treatment for cancers. Study to this end is on the way in prostate cancer and the results are encouraging. FlnA has been studied in large categories of cancers, such as prostate cancer, breast cancer, melanoma, lung cancer, etc. However, most studies did not evaluate the differences that arise from the localization of the protein, which was a great pity! What’s more, although FlnA’s is undoubtedly important in cancer invasion and metastasis, both preclinical and clinical researches are very rare in some highly metastatic cancers, such as pancreatic cancer. In this mini-review, we give a comprehensive summary of FlnA’ s expression in cancers. Where available, we also indicate the correlation of FlnA with cancer stages and patient prognosis, and clarify its localization (nucleus/cytoplasm) and its dual role (promote/suppress) in different cancers.
KeywordsFilamin A Cancer metastasis Localization Nucleus Cytoplasm
Prostate-specific membrane antigen
Human androgen receptor
Androgen deprivation therapy
Castration-resistant prostate cancer
Renal cell carcinoma
Epidermal growth factor receptor
This work was supported by National High Technology Research and Development Program (863 Program, 2014AA020609), China.
Conflicts of Interest
The authors have no conflict of interest.
- 3.Robertson SP (2005) Filamin A: phenotypic diversity. Curr Opin Genet Dev 15:301–307.Google Scholar
- 5.Savoy RM, Ghosh PM (2013) The dual role of filamin A in cancer: can’t live with (too much of) it, can’t live without it. Endocr Relat Cancer 20:R341–R356.Google Scholar
- 27.Takabayashi T, Xie MJ, Takeuchi S, Kawasaki M, Yagi H, Okamoto M, et al. (2010) LL5bdirects the translocation of filamin A and SHIP2 to sites of phosphatidylinositol 3,4,5-triphosphate (PtdIns(3,4,5)P3) accumulation, and PtdIns(3,4,5)P3 localization is mutually modified by co-recruited SHIP2. J Biol Chem 285:16155–16165CrossRefPubMedPubMedCentralGoogle Scholar
- 28.Gawecka JE, Griffiths GS, Ek-Rylander B, Ramos JW, Matter ML (2010) R-Ras regulates migration through an interaction with filamin A in melanoma cells. PLoS ONE 5:e11269.Google Scholar
- 35.Gopalakrishnapillai Anilkumar, Sigrid A. Rajasekaran, Song Wang, Oliver Hankinson, Neil H. Bander, Rajasekaran AK et al. (2003) Prostate-specific membrane antigen association with filamin A modulates its internalization and NAALADase activity. Cancer Res 63:2645–2648.Google Scholar
- 44.Mooso BA, Vinall RL, Tepper CG, Savoy RM, Cheung JP, Singh S, et al. (2012) Enhancing the effectiveness of androgen deprivation in prostate cancer by inducing filamin A nuclear localization. Endocr Relat Cancer 19:795–777Google Scholar
- 52.Alper O, Stetler-Stevenson WG, Harris LN, Leitner WW, Ozdemirli M, Hartmann D, et al. (2009) Novel anti-filamin-A antibody detects a secreted variant of filamin-A in plasma from patients with breast carcinoma and high-grade astrocytoma. Cancer Sci 100:1748–1756CrossRefPubMedPubMedCentralGoogle Scholar
- 53.Tian H-M, Liu X-H, Han W, Zhao L-L, Yuan B, Yuan C-J (2013) Differential expression of filamin A and its clinical significance in breast cancer. Oncol Lett 6:6681–6686.Google Scholar
- 58.Keshamouni VG, Michailidis G, Grasso CS, Anthwal S, Strahler JR, Walker A, et al. (2006) Differential protein expression profiling by iTRAQ-2DLC-MS/MS of lung cancer cells undergoing epithelial-mesenchymal transition reveals a migratory/invasive phenotype. J Proteome Res 5:1143–1154CrossRefPubMedGoogle Scholar
- 59.Nallapalli RK, Ibrahim MX, Zhou AX, Bandaru S, Sunkara SN, Redfors B, et al. (2012) Targeting filamin A reduces K-RAS–induced lung adenocarcinomas and endothelial response to tumor growth in mice. Mol Cancer 11:50.Google Scholar
- 69.Guedj N, Zhan Q, Perigny M, Rautou PE, Degos F, Belghiti J, et al. (2009) Comparative protein expression profiles of hilar and peripheral hepatic cholangiocarcinomas. J Hepatol 5:193–101Google Scholar