The dual role of filamin A in cancer: can't live with (too much of) it, can't live without it.
The dual role of filamin A in cancer: can't live with (too much of) it, can't live without it.
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DOI：
10.1530/erc-13-0364
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发表时间：
2013-12
影响因子：
3.9
通讯作者：
Ghosh PM
中科院分区：
文献类型：
--
作者：
Savoy RM;Ghosh PM
细丝蛋白A（Filamin A，FlnA）与肌动蛋白（actin）结合，是细胞骨架的调节因子。最近，它在细胞中的作用因FlnA参与癌症发展而受到审查。FlnA最初被发现是一种促癌蛋白，参与侵袭和转移。然而，最近的研究也发现，在某些条件下，它阻止了肿瘤的形成或进展，混淆了FlnA在癌症发展中的确切功能。在这里，我们试图破译FlnA在癌症中的作用及其双重作用的影响。我们认为FlnA亚细胞定位的差异决定了其在癌症发展中的作用。在细胞质中，FlnA除了参与细胞迁移和粘附途径如R-Ras和整联蛋白信号传导外，还在各种生长信号传导途径如血管内皮生长因子中起作用。参与这些途径和各种其他途径已经显示出高细胞质FlnA水平与侵袭性癌症之间的相关性。然而，FlnA的活性切割形式可以定位于细胞核而不是细胞质，并且它与转录因子的相互作用与癌症侵袭性的降低有关。因此，仅当FlnA定位于细胞质时，FlnA的过表达才具有肿瘤促进作用，而如果FlnA经历蛋白水解并且所得的C末端片段定位于细胞核，则其起到抑制肿瘤生长和抑制转移的作用。开发靶向FlnA并引起裂解和随后定位于细胞核的药物可能是治疗癌症的新的和有效的研究领域。
Filamin A (FlnA) has been associated with actin as cytoskeleton regulator. Recently its role in the cell has come under scrutiny for FlnA’s involvement in cancer development. FlnA was originally revealed as a cancer-promoting protein, involved in invasion and metastasis. However, recent studies have also found that under certain conditions, it prevented tumor formation or progression, confusing the precise function of FlnA in cancer development. Here, we try to decipher the role of FlnA in cancer and the implications for its dual role. We propose that differences in subcellular localization of FlnA dictate its role in cancer development. In the cytoplasm, FlnA functions in various growth signaling pathways, such as vascular endothelial growth factor, in addition to being involved in cell migration and adhesion pathways, such as R-Ras and integrin signaling. Involvement in these pathways and various others has shown a correlation between high cytoplasmic FlnA levels and invasive cancers. However, an active cleaved form of FlnA can localize to the nucleus rather than the cytoplasm and its interaction with transcription factors has been linked to a decrease in invasiveness of cancers. Therefore, overexpression of FlnA has a tumor-promoting effect, only when it is localized to the cytoplasm, whereas if FlnA undergoes proteolysis and the resulting C-terminal fragment localizes to the nucleus, it acts to suppress tumor growth and inhibit metastasis. Development of drugs to target FlnA and cause cleavage and subsequent localization to the nucleus could be a new and potent field of research in treating cancer.
影响因子：
1.8
作者：
Douvaras P;Liu W;Mort RL;McKie L;West KM;Cross SH;Morley SD;West JD
通讯作者：
West JD