纪念斯隆-凯特琳癌症中心科研人员发现与肺癌转移、扩散、复发有关的两个重要基因，相关研究论文发表在最新一期Cell上面。研究人员发现，WNT信号转导途径不仅参与结肠癌扩散，还能增强早期肺癌细胞转移到其他器官并定殖的能力。并不是所有肺癌细胞在确诊之前已经扩散，因此研究人员推测肺癌转移可能源于一些基因突变启动了癌细胞转移。
研究人员利用生物信息学方法筛查大量肺癌样本发现， Wnt信号转导通路是6个经筛查的信号转导路径中唯一一个在肺癌细胞和已扩散肺癌细胞中保持高活性的通路。他们还指出， Wnt信号转导通路与恶性癌症的发生有密切关系。
“基因突变激活Wnt信号通路一般会导致结肠癌的发生，肺癌通常是由其他基因变异引起，所以我们对于Wnt细胞信号转导通路与肺癌有莫大关系也非常惊讶。”论文通讯作者琼·马萨格博士表示。
实验证明通常引起肺癌发生的KRAS和EGFR基因变异也与Wnt信号转导通路相关。进一步研究发现HOXB9和LEF1基因经Wnt信号转导通路激活后可增加肺癌细胞转移和定殖的能力。因此，实验证明Wnt信号转导通路与肺癌的转移、扩散、复发密切相关。（生物谷Bioon.com）
生物谷推荐原始出处：
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.
