A National Health Research Institutes (NHRI) research team has discovered a key mechanism that affects lung cancer metastasis, which could become a potential biomarker, the institutes said yesterday.
Cancer has been the leading cause of death in Taiwan for 37 years, with lung cancer the leading cause of cancer deaths. A significant majority of such deaths are associated with tumor metastasis.
A team led by NHRI Immunology Research Center director Tan Tse-hua (譚澤華) and assistant research fellow Chuang Huai-chia (莊懷佳) has spent years exploring the mechanism between cancer metastasis and MAP4K3 (also known as GLK), a protein encoded by the MAP4K3 gene.
The team’s previous studies showed that up to 76 percent of non-small cell lung cancer patients have overexpression of GLK in their bodies, and that overexpression of GLK in human lung cancer is associated with poor prognosis and recurrence, Chuang said.
However, the role of GLK in cancer recurrence was unclear, she said.
Using GLK transgenic mice that were bred with genetically modified lung cancer mice allowed the team to study the effect of GLK on the progression of the disease, and they found that GLK induced lung cancer to metastasize in lymph nodes, the brain and liver, she said.
Transgenic GLK promotes tumor metastasis and cell migration through the scaffold protein IQ motif–containing GTPase-activating protein 1 (IQGAP1), by binding to, phosphorylating and activating IQGAP1, the team found.
Human tissues displayed increased phospho-IQGAP1, which correlated with poor survival, so if the overexpression of GLK is inhibited, lung cancer recurrence and tumor metastasis might be controlled, she added.
Tan said that GLK plays a crucial role in promoting cell migration and cancer metastasis by directly binding to and phosphorylating IQGAP1, so their findings suggest that the GLK–IQGAP1 complex is a potential therapeutic target for cancer recurrence.
GLK knockout (inactivated) mice have a life span about 1.5 times that of average mice, which suggests that GLK inhabitation might also have anti-aging effects, he said.
The study was published as the cover story in last month’s issue of Cancer Research and the team is applying for a patent for the findings of the GLK–IQGAP1 complex study, the NHRI said.
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