The vast majority of deadly lung cancer cases (85 percent) are termed non-small-cell lung carcinomas (NSCLCs), which often contain a mutated gene called LKB1.
The vast majority of deadly lung cancer cases (85 percent) are termed non-small-cell lung carcinomas (NSCLCs), which often contain a mutated gene called LKB1. Salk Institute researchers have now discovered precisely why inactive LKB1 results in cancer development. The surprising results, published in the online version of Cancer Discovery on July 26, 2019, highlight how LBK1 communicates with two enzymes that suppress inflammation in addition to cell growth, to block tumor growth. The findings could lead to new therapies for NSCLC.
“For the first time, we’ve found specific direct targets for LKB1 that prevent lung cancer and discovered—very unexpectedly—that inflammation plays a role in this tumor growth,” says Professor Reuben Shaw, director of the Salk Cancer Center and senior author of the paper. “With this knowledge we can hopefully develop new treatments for this large fraction of lung cancer patients.”
When functioning normally, LKB1 acts as a tumor suppressor, actively preventing cancer from forming in the first place. Scientists knew that the LKB1 gene worked like the captain of a relay team, passing cellular signals, like a baton, to enzymes called kinases, that then passed the signal to other enzymes in a chain reaction. LKB1 acts as the captain of a team consisting of 14 different kinase teammates. But which of these kinases is specifically responsible for carrying on LKB1’s tumor suppressive function has been unclear for the more than 15 years since LKB1 was first identified as a major gene disrupted in lung cancer. In 2018, the Shaw lab solved the first step of this molecular whodunnit by showing that 2 of the 14 teammates (the main enzymes known to control metabolism and growth) were surprisingly not as important to LKB1’s effects to block lung cancer as most scientists had assumed. That left 12 of their kinase teammates as potentially important, but almost nothing was known about them.
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