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Mechanism May Explain Quick Metastases of Lung Cancer

Last Updated: July 06, 2009.

In patients with lung cancer, the WNT/TCF cell-signaling pathway appears to play a major role in the spread of the disease to the brain and bone, according to a study published online July 2 in Cell.

MONDAY, July 6 (HealthDay News) -- In patients with lung cancer, the WNT/TCF cell-signaling pathway appears to play a major role in the spread of the disease to the brain and bone, according to a study published online July 2 in Cell.

Don X. Nguyen, Ph.D., of the Memorial Sloan-Kettering Cancer Center in New York City, and colleagues used bioinformatics to analyze collections of lung tumor samples, tested six cell-signaling pathways, and found that only the WNT/TCF cell-signaling pathway was hyperactive in lung tumors that metastasized.

In subsequent experiments in mice, the researchers found that a hyperactive WNT/TCF pathway activated tumor-promoting mutations in the genes KRAS and EGFR, as well as two genes -- HOXB9 and LEF1 -- associated with lung cancer metastasis.

"While not without limitations, our experimental systems recapitulate important phenotypic and molecular features of lung adenocarcinoma, including brain and bone metastasis, and a hyperactive WNT/TCF pathway in the background of relevant oncogenic mutations," the authors conclude. "This model may be useful for achieving a deeper understanding of early metastatic events and the development of improved treatments for lung adenocarcinoma patients at risk for metastasis."

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