紀(jì)念斯隆-凱特琳癌癥中心科研人員發(fā)現(xiàn)與肺癌轉(zhuǎn)移、擴(kuò)散,、復(fù)發(fā)有關(guān)的兩個(gè)重要基因，相關(guān)研究論文發(fā)表在最新一期Cell上面。研究人員發(fā)現(xiàn),，WNT信號轉(zhuǎn)導(dǎo)途徑不僅參與結(jié)腸癌擴(kuò)散，還能增強(qiáng)早期肺癌細(xì)胞轉(zhuǎn)移到其他器官并定殖的能力,。并不是所有肺癌細(xì)胞在確診之前已經(jīng)擴(kuò)散,，因此研究人員推測肺癌轉(zhuǎn)移可能源于一些基因突變啟動了癌細(xì)胞轉(zhuǎn)移。
研究人員利用生物信息學(xué)方法篩查大量肺癌樣本發(fā)現(xiàn),， Wnt信號轉(zhuǎn)導(dǎo)通路是6個(gè)經(jīng)篩查的信號轉(zhuǎn)導(dǎo)路徑中唯一一個(gè)在肺癌細(xì)胞和已擴(kuò)散肺癌細(xì)胞中保持高活性的通路,。他們還指出,， Wnt信號轉(zhuǎn)導(dǎo)通路與惡性癌癥的發(fā)生有密切關(guān)系。
“基因突變激活Wnt信號通路一般會導(dǎo)致結(jié)腸癌的發(fā)生,，肺癌通常是由其他基因變異引起,，所以我們對于Wnt細(xì)胞信號轉(zhuǎn)導(dǎo)通路與肺癌有莫大關(guān)系也非常驚訝。”論文通訊作者瓊·馬薩格博士表示,。
實(shí)驗(yàn)證明通常引起肺癌發(fā)生的KRAS和EGFR基因變異也與Wnt信號轉(zhuǎn)導(dǎo)通路相關(guān),。進(jìn)一步研究發(fā)現(xiàn)HOXB9和LEF1基因經(jīng)Wnt信號轉(zhuǎn)導(dǎo)通路激活后可增加肺癌細(xì)胞轉(zhuǎn)移和定殖的能力。因此,，實(shí)驗(yàn)證明Wnt信號轉(zhuǎn)導(dǎo)通路與肺癌的轉(zhuǎn)移,、擴(kuò)散、復(fù)發(fā)密切相關(guān),。（生物谷Bioon.com）
生物谷推薦原始出處：
Cell, 02 July 2009 doi:10.1016/j.cell.2009.04.030
WNT/TCF Signaling through LEF1 and HOXB9 Mediates Lung Adenocarcinoma Metastasis
Don X. Nguyen1,Anne C. Chiang2,Xiang H.-F. Zhang1,Juliet Y. Kim1,Mark G. Kris2,5,Marc Ladanyi3,4,William L. Gerald3,4andJoan Massagué1,6,,
1 Cancer Biology and Genetics Program, Memorial Sloan-Kettering Cancer Center, New York, NY, USA
2 Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, NY, USA
3 Department of Pathology, Memorial Sloan-Kettering Cancer Center, New York, NY, USA
4 Human Oncology and Pathogenesis Program, Memorial Sloan-Kettering Cancer Center, New York, NY, USA
5 Weill Medical College of Cornell University, Memorial Sloan-Kettering Cancer Center, New York, NY, USA
6 Howard Hughes Medical Institute, Memorial Sloan-Kettering Cancer Center, New York, NY, USA
Metastasis from lung adenocarcinoma can occur swiftly to multiple organs within months of diagnosis. The mechanisms that confer this rapid metastatic capacity to lung tumors are unknown. Activation of the canonical WNT/TCF pathway is identified here as a determinant of metastasis to brain and bone during lung adenocarcinoma progression. Gene expression signatures denoting WNT/TCF activation are associated with relapse to multiple organs in primary lung adenocarcinoma. Metastatic subpopulations isolated from independent lymph node-derived lung adenocarcinoma cell lines harbor a hyperactive WNT/TCF pathway. Reduction of TCF activity in these cells attenuates their ability to form brain and bone metastases in mice, independently of effects on tumor growth in the lungs. The WNT/TCF target genes HOXB9 and LEF1 are identified asmediators of chemotactic invasion and colony outgrowth. Thus, a distinct WNT/TCF signaling program through LEF1 and HOXB9 enhances the competence of lung adenocarcinoma cells to colonize the bones and the brain.
