▲ (from the left) Professor Hun Sik Kim of the Department of Microbiology and Professor Chang Ohk Sung of the Department of Pathology

A research team led by Professor Hun Sik Kim of the Department of Microbiology and Professor Chang Ohk Sung of the Department of Pathology at Asan Medical Center recently became the first to establish that overexpression of HPK1, a specific protein of natural killer (NK) cells, causes NK cells to lose their function during cancer metastasis process, thereby promoting cancer metastasis. To prevent cancer metastasis, the immune system needs to be activated, and NK cells play a key role in this. Previous studies have shown that the loss of NK cell function could promote cancer metastasis, but the mechanism remained unknown.

While the research team was searching for therapeutic targets to restore NK cell function, they discovered that NK cell function in the blood and metastatic sites is lost and HPK1 is overexpressed during cancer metastasis. To verify this in reverse, they genetically modified mice to overexpress HPK1 in NK cells and injected melanoma cancer cells into their veins to analyze the trend of lung metastasis according to HPK1 expression levels.

The results showed that HPK1 overexpression promotes metastasis to various organs, not just the lungs. Notably, HPK1 was found to influence metastatic cancer more than primary cancer. On the other hand, HPK1 deficiency activated NK cell function, effectively suppressing cancer metastasis and further enhancing the therapeutic effects of immune checkpoint inhibitors. This confirmed that HPK1 regulation is a promising target for treating metastatic cancer in practice.

This study was recently published in the prestigious academic journal, ‘Advanced Science.’