A research team at the National Cancer Center (NCC) Graduate School of Cancer Science and Policy has uncovered new drug targets that can simultaneously control multiple oncogenes.
The main reason for developing cancer is due to the overexpression of various oncogenes. Targeted anticancer drugs used in clinical trials mostly aim one or two oncogenes, so the treatment cannot cure cancer that grows by depending on other carcinogenic genes than the target. Genetic information on the nucleus chromosome is transferred to messenger ribonucleic acid (mRNA), and mRNA then crosses the nuclear membrane and travels to the protein synthesis plant in the cytosol.
|Professor Lee Byung-il of the National Cancer Center Graduate School of Cancer Science and Policy|
The research team, led by Professors Lee Byung-il and Jang Hyon-chol, found that a protein complex called Apoptosis inhibitor 5 (API5) and Fibroblast Growth Factor 2 (FGF2) plays a crucial role in controlling mRNA migration of essential carcinogenic genes such as c-Myc and Cyclin D1 (CCND1).
The API5 gene is overexpressed in various cancers, including cervical, lung, breast, and pancreatic cancer, and is responsible for apoptosis suppression. The FGF2 is a proliferation factor secreted out of the cell but is also present in a large amount in the cell nucleus.
The research team identified the three-dimensional structure of the complex of API5 and FGF2 by X-ray crystallography and found a group of proteins that bind to the API5-FGF2 complex using liquid chromatography-mass spectrometry.
The obtained information was analyzed by bioinformatics techniques and proved that the API5-FGF2 complex is involved in the migration of mRNA from the cell nucleus to the cytoplasm.
In particular, when the binding of API5 and FGF2 was inhibited, the number of proteins of oncogenes, such as c-Myc and CCND1, in cancer cells significantly lowered.
The research was published in Nucleic Acids Research, an international journal of Oxford University Press, with a high impact factor of 11.147, on May 7.
The team also applied for the related original patent.
A follow-up study to discover new candidate substance of anticancer drug that targets API5-FGF2 is going on. The research was conducted with the financial support of NCC and the National Research Foundation of Korea.