2024-02-22 15:00:00
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Smoking and drinking are known to increase the load of free radicals 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.
KAIST announced on the 21st that Professor Jun Kim’s research team at the Graduate School of Medical Sciences has identified a new mechanism by which smoking and drinking, which are carcinogenic risk factors, are involved in the occurrence and growth of oral cancer.
In this study, the research team uncovered a pathway in which smoking and drinking 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, thereby securing new clues for the development of anticancer drugs.
Increased YAP expression and dimer formation of TM4SF19 protein due to oxidative stress in oral cancer cells. Source: KAIST
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. It was revealed through protein biochemistry experiments using oral cancer cell lines that this protein forms a dimer substance formed by polymerizing 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. Inhibiting this protein (TM4SF19) in oral cancer cells reduced oncogene (YAP) expression, which had the effect of reducing the proliferation and metastatic ability of cancer cells.
Decreased YAP expression and tumor reduction by TM4SF19 reduction. Source: KAIST
Professor Jun Kim of KAIST Graduate School of Medical Sciences said, “This study is significant in that it not only identified a new molecular mechanism by which smoking and drinking promote cancer development, but also suggested a new direction for oral cancer research and discovered a new drug target protein (TM4SF19). “There is,” he explained the significance of the study.
The results of the study were published on February 5 in the international academic journal Proceedings of the National Academy of Sciences (PNAS).
논문명: TM4SF19 controls GABP-dependent YAP transcription in head and neck cancer under oxidative stress conditions
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