転移と言えばMassaguéです・・・

MassaguéさんがCellにまたまた転移関連論文を出した。WNT/TCFシグナルと肺転移であるが、先のNat Geneticsのrs6983267論文といい、近年の包括的癌関連遺伝子解析の結果が収斂しつつある感が強い。重要な遺伝子シグナルとしてはWNT/TCFシグナルがやはりpivotalであるということなのかな・・・・


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. Kris²Marc Ladanyi³William L. Gerald,Joan Massagué

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

Summary

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.