Cancer Res：英研究发现与口腔癌相关蛋白质

近日，英国研究人员发现了一种在口腔癌中起关键作用的蛋白质，以它为靶点进行治疗可以延长患癌实验鼠的生命。这一发现有望为人类带来口腔癌新疗法。

英国癌症研究会等机构的研究人员在美国新一期《癌症研究》(Cancer Research)杂志上报告说，他们发现名为FRMD4A的蛋白质在口腔癌中起着关键作用。这种蛋白质会促进癌细胞生长，机体中这种蛋白质的含量越高，癌症就越容易扩散，或是越容易在治疗后复发。

研究人员接下来开展的动物实验显示，如果使用药物阻碍这种蛋白质的功能，则癌细胞的生长会被抑制，患有口腔癌实验鼠的生命得以延长。

研究人员斯蒂芬·戈尔迪表示，现在已有的一些药物可以用来对付蛋白质FRMD4A，因此有望很快在本次研究的基础上展开人类临床试验。对于使用传统手术和化疗不奏效的口腔癌患者来说，这有望成为他们新的治疗选择。

据介绍，过去虽然出现了一些口腔癌新疗法，但口腔癌患者的生存率在过去30年中并没有出现明显改善，本次研究成果有望为此带来新希望。

doi:10.1158/0008-5472.CAN-12-0423
PMC:
PMID:

FRMD4A Upregulation in Human Squamous Cell Carcinoma Promotes Tumor Growth and Metastasis and Is Associated with Poor Prognosis

Stephen J. Goldie1, Klaas W. Mulder1, David Wei-Min Tan2, Scott K. Lyons1, Andrew H. Sims3, and Fiona M. Watt1,2

New therapeutic strategies are needed to improve treatment of head and neck squamous cell carcinoma (HNSCC), an aggressive tumor with poor survival rates. FRMD4A is a human epidermal stem cell marker implicated previously in epithelial polarity that is upregulated in SCC cells. Here, we report that FRMD4A upregulation occurs in primary human HNSCCs where high expression levels correlate with increased risks of relapse. FRMD4A silencing decreased growth and metastasis of human SCC xenografts in skin and tongue, reduced SCC proliferation and intercellular adhesion, and stimulated caspase-3 activity and expression of terminal differentiation markers. Notably, FRMD4A attenuation caused nuclear accumulation of YAP, suggesting a potential role for FRMD4A in Hippo signaling. Treatment with the HSP90 inhibitor 17-DMAG or ligation of CD44 with hyaluronan caused nuclear depletion of FRMD4A, nuclear accumulation of YAP and reduced SCC growth and metastasis. Together, our findings suggest FRMD4A as a novel candidate therapeutic target in HNSCC based on the key role in metastatic growth we have identified.