近日，英國研究人員發(fā)現(xiàn)了一種在口腔癌中起關(guān)鍵作用的蛋白質(zhì),，以它為靶點(diǎn)進(jìn)行治療可以延長患癌實(shí)驗(yàn)鼠的生命,。這一發(fā)現(xiàn)有望為人類帶來口腔癌新療法。
英國癌癥研究會(huì)等機(jī)構(gòu)的研究人員在美國新一期《癌癥研究》(Cancer Research)雜志上報(bào)告說,，他們發(fā)現(xiàn)名為FRMD4A的蛋白質(zhì)在口腔癌中起著關(guān)鍵作用,。這種蛋白質(zhì)會(huì)促進(jìn)癌細(xì)胞生長，機(jī)體中這種蛋白質(zhì)的含量越高,，癌癥就越容易擴(kuò)散,，或是越容易在治療后復(fù)發(fā)。
研究人員接下來開展的動(dòng)物實(shí)驗(yàn)顯示,，如果使用藥物阻礙這種蛋白質(zhì)的功能,，則癌細(xì)胞的生長會(huì)被抑制，患有口腔癌實(shí)驗(yàn)鼠的生命得以延長,。
研究人員斯蒂芬·戈?duì)柕媳硎?，現(xiàn)在已有的一些藥物可以用來對付蛋白質(zhì)FRMD4A，因此有望很快在本次研究的基礎(chǔ)上展開人類臨床試驗(yàn),。對于使用傳統(tǒng)手術(shù)和化療不奏效的口腔癌患者來說,，這有望成為他們新的治療選擇。
據(jù)介紹,，過去雖然出現(xiàn)了一些口腔癌新療法,，但口腔癌患者的生存率在過去30年中并沒有出現(xiàn)明顯改善，本次研究成果有望為此帶來新希望,。 （生物谷Bioon.com）
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.
