Professor Jun Kim’s research group from the Graduate School of Medical Sciences
Gain clues to developing anticancer drugs for oral cancer
Increased YAP expression and TM4SF19 protein dimer formation due to oxidative stress in oral cancer cells.
[정보통신신문=박남수기자]
Smoking and drinking are known to increase the free radical load in cells and cause high levels of oxidative stress. However, the specific mechanism by which oxidative stress promotes the development of oral cancer has not yet been clearly identified.
The Korea Advanced Institute of Science and Technology (KAIST) announced on the 21st that Professor Jun Kim’s research group at the Graduate School of Medical Sciences has identified a new mechanism by which smoking and alcohol, which are factors of cancer risk, are involved in the onset of cancer and growth of oral cancer.
In this study, the research team discovered a pathway in which smoking and alcohol promote the growth of oral cancer not only through direct DNA damage but also through transcriptional regulation (increased expression of oncogenic genes) through oxidative stress, thus providing new clues for the development of anticancer drugs.
The research team focused on the TM4SF19 (Transmembrane 4 L Six Family Member 19) protein, which is specifically and highly expressed in oral cancer patients. Through protein biochemistry experiments using oral cancer cell lines it was revealed that this protein forms a dimeric substance formed by the polymerization of two molecules due to oxidative stress, temporarily increasing the expression of YAP (yes-associated protein), a known carcinogen . This protein (TM4SF19) is expressed at low levels in most normal tissues and has an unknown function. Inhibition of this protein (TM4SF19) in oral cancer cells reduced the expression of the oncogene (YAP), which had the effect of reducing the proliferation and metastatic capacity of the cancer cells.
Professor Jun Kim from the KAIST Graduate School of Medical Sciences said: “This study is significant as it has not only identified a new molecular mechanism by which smoking and drinking promote the development of cancer, but has also suggested a new direction for oral cancer research and discovered a new drug target protein (TM4SF19). “It exists,” he explained the importance of the study.
This study, in which postdoctoral researcher Eunbi Shin, a graduate of the KAIST Graduate School of Medical Sciences, participated as first author, was published on February 5 in the international academic journal “PNAS”. (Article Title: TM4SF19 Controls GABP-Dependent YAP Transcription in Head and Neck Cancer Under Oxidative Stress Conditions)
Meanwhile, this study was conducted with the support of the Mid-Career Researchers Support Project of the Korean National Research Foundation.
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