Department of Cancer Studies and Molecular Medicine, University of Leicester, Leicester, UK.
Oncogene. 2012 Mar 22;31(12):1493-503. doi: 10.1038/onc.2011.336. Epub 2011 Aug 8.
Fos-related antigen 1 (Fra-1) is a Fos family member overexpressed in several types of human cancers. Here, we report that Fra-1 is highly expressed in the muscle-invasive form of the carcinoma of the bladder (80%) and to a lesser extent in superficial bladder cancer (42%). We demonstrate that in this type of cancer Fra-1 is regulated via a C-terminal instability signal and C-terminal phosphorylation. We show that manipulation of Fra-1 expression levels in bladder cancer cell lines affects cell morphology, motility and proliferation. The gene coding for AXL tyrosine kinase is directly upregulated by Fra-1 in bladder cancer and in other cell lines. Importantly, our data demonstrate that AXL mediates the effect of Fra-1 on tumour cell motility but not on cell proliferation. We suggest that AXL may represent an attractive therapeutic target in cancers expressing high Fra-1 levels.
Fos 相关抗原 1（Fra-1）是 Fos 家族成员在几种类型的人类癌症中过表达。在这里，我们报告 Fra-1 在肌肉浸润性膀胱癌（80%）中高度表达，在浅表膀胱癌中表达程度较低（42%）。我们证明 Fra-1 在这种类型的癌症中受到 C 末端不稳定性信号和 C 末端磷酸化的调节。我们表明，在膀胱癌细胞系中操纵 Fra-1 的表达水平会影响细胞形态、运动性和增殖。编码 AXL 酪氨酸激酶的基因在膀胱癌和其他细胞系中被 Fra-1 直接上调。重要的是，我们的数据表明 AXL 介导 Fra-1 对肿瘤细胞运动性的影响，但不影响细胞增殖。我们认为 AXL 可能代表高 Fra-1 水平表达的癌症的一个有吸引力的治疗靶点。
