'Tumor suppressor' gene appears to promote aggressive type of lung cancer

Thomas Jefferson U.'s Bo Lu

A gene found to be conserved across many species, called Nitrilase 1 (Nit1), was traditionally thought to act as a tumor suppressor by preventing the aggressive growth of cancers.

Now researchers from Thomas Jefferson University say this highly active gene in human lung cancer is acting in the opposite way and instead promoting cancer growth. And the results of this study may give rise to a new drug target for an increasingly drug-resistant type of lung cancer.

Scientists at the Sidney Kimmel Cancer Centre (Thomas Jefferson University) published their work in the journal Oncotarget earlier this month.

They identified the controversial role of Nit1 by showing the gene is significantly upregulated in common lung cancer, as compared to normal cells, and importantly when it is genetically silenced the growth of the lung tumor is halted.

"Lung cancer in most patients is becoming increasingly resistant to the therapies that exist today, making lung cancer the leading cause of cancer death worldwide," said Bo Lu who is the senior author of the study. "There is a critical need for new agents, and an inhibitor of Nit1 may represent a new drug strategy."

The researchers used a lung cancer mouse model where a KRAS mutation (a mutation that causes an aggressive form of lung cancer in humans) induced the mouse to develop lung cancer. Next they genetically silenced Nit1 and from this they observed the resulting tumors were 5 times smaller than a KRAS mouse with normal copies of the gene Nit1.  

They also tested a common chemotherapy, called cisplatin, in mice lacking Nit1 and saw an increased sensitivity to the chemotherapy. "The cancer was significantly more sensitive to cisplatin when Nit1 was silenced

"This is a story of discoveries--a tale of a false assumption that has led to a possible new drug strategy," said Lu.

- here's the release

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