乳酸脱氢酶A
头颈部鳞状细胞癌
癌症研究
瓦博格效应
组蛋白乙酰转移酶
基因沉默
乙酰化
转移
癌症
生物
P300-CBP转录因子
乳酸脱氢酶
糖酵解
癌细胞
头颈部癌
内分泌学
酶
生物化学
组蛋白乙酰转移酶
新陈代谢
基因
遗传学
作者
Ying Lu,Yong Wang,Leilei Zhang,Zhen Ma,Kaitao Yu,Shu Yao,Xuan Zou,Jiarong Yang,Xin Liu,Chenglong Wang,Yong Du,Qihong Li
标识
DOI:10.1016/j.canlet.2024.216869
摘要
Lysine acetyltransferase 7 (KAT7), a histone acetyltransferase, has recently been identified as an oncoprotein and has been implicated in the development of various malignancies. However, its specific role in head and neck squamous carcinoma (HNSCC) has not been fully elucidated. Our study revealed that high expression of KAT7 in HNSCC patients is associated with poor survival prognosis and silencing KAT7 inhibits the Warburg effect, leading to reduced proliferation, invasion, and metastatic potential of HNSCC. Further investigation uncovered a link between the high expression of KAT7 in HNSCC and tumor-specific glycolytic metabolism. Notably, KAT7 positively regulates Lactate dehydrogenase A (LDHA), a key enzyme in metabolism, to promote lactate production and create a conducive environment for tumor proliferation and metastasis. Additionally, KAT7 enhances LDHA activity and upregulates LDHA protein expression by acetylating the lysine 118 site of LDHA. Treatment with WM3835, a KAT7 inhibitor, effectively suppressed the growth of subcutaneously implanted HNSCC cells in mice. In conclusion, our findings suggest that KAT7 exerts pro-cancer effects in HNSCC by acetylating LDHA and may serve as a potential therapeutic target. Inhibiting KAT7 or LDHA expression holds promise as a therapeutic strategy to suppress the growth and progression of HNSCC.
科研通智能强力驱动
Strongly Powered by AbleSci AI