Mutated Signaling Pathway Triggers Lung Cancer Metastasis

Cancer researchers have found that in addition to the mutations that cause lung cancer, these cells require another mutation to metastasize and spread to other tissues.

Lung cancers (adenocarcinomas) commonly result from mutations in the KRAS and EGFR genes. Yet, cancer cells with only these mutations do not usually spread beyond the lungs.

To determine what genetic signals would be required to drive metastasis in lung tumors investigators at Memorial Sloan-Kettering Cancer Center (New York, NY, USA) employed bioinformatic techniques to screen numerous lung tumor samples. They reported in the July 2, 2009, online edition of the journal Cell that the WNT cell-signaling pathway - a common cause of colon cancer when mutated - was the only one of six pathways tested that was hyperactive in lung tumors that went on to metastasize but was normal in those that did not spread.

The WNT pathway targets the HOXB9 and LEF1 genes, which have been identified as mediators of chemotactic invasion and colony outgrowth.

"Mutations that activate the WNT pathway are a common cause of colon cancer, but lung tumors are initiated by mutations in other genes, so we were surprised that a hyperactive WNT pathway would be responsible for metastasis in lung cancer," said senior author Dr. Joan Massagué, professor of cell biology and genetics at Memorial Sloan-Kettering Cancer Center. "Our findings suggest that using treatments that target the WNT pathway may help prevent lung cancer from repeatedly seeding itself throughout the vital organs of patients at risk for metastasis."

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Memorial Sloan-Kettering Cancer Center