A lack of oxygen is actually beneficial for cancer survival. This is because the 'HIF1α' protein produced by cells when oxygen is scarce enhances the invasiveness of cancer. Domestic researchers have clarified a physiological circuit that strengthens the metastatic ability of cancer cells by emitting false signals of oxygen deficiency and have found a way to prevent cancer metastasis.
Professor Kang Byeong-heon and his research team from Ulsan National Institute of Science and Technology (UNIST) discovered a circuit in melanoma cells, a type of skin cancer, that induces metastasis by signaling as if oxygen is deficient despite sufficient oxygen being present, and they demonstrated that this can be blocked by reactivating the protein CypD, he noted on the 27th. This research was published online on July 24 in the international journal 'Signal Transduction and Targeted Therapy.'
The HIF1α protein is originally activated when oxygen is deficient and aids in cell survival. However, when this protein is overly expressed in cancer cells, it enables the cells to move more easily and create new blood vessels, allowing them to spread into surrounding tissues.
According to the researchers, melanoma uses 'reactive oxygen species (ROS)' as a false signal of oxygen deficiency. Melanoma is a cancer type that metastasizes very well. Even in environments where oxygen is abundant for actual cancer cells, if there are high levels of ROS within the cell mitochondria, the amount of HIF1α protein increases.
Based on this, they also found a way to cut off the false hypoxic signaling circuit in melanoma cells. By activating the CypD protein, when CypD is activated, the 'mitochondrial permeability transition pore (mPTP)' opens, preventing excessive accumulation of ROS within the cells. In a state where ROS accumulates, the action of enzymes that induce the degradation of HIF1α protein is suppressed.
In animal experiments, when a gene carrier (Ad-CypD) that can overexpress the CypD protein was locally administered to skin cancer tissues, metastasis to the lymph nodes and lungs was effectively blocked. Meanwhile, there was no impact on the size of the primary tumor on the skin surface.
Professor Kang Byeong-heon stated, 'Melanoma is located on the skin surface, making drug injection easier, which increases the applicability of localized gene therapy,' and emphasized, 'The CypD-based gene therapy proposed in this study is expected to effectively suppress metastasis while directly attacking cancer cells, potentially achieving a synergy when used in conjunction with existing immune anticancer agents.' The research team is currently conducting follow-up studies to develop the results of this research into a new cancer treatment method.
References
Signal Transduction and Targeted Therapy (2025), DOI: https://doi.org/10.1038/s41392-025-02314-8