ACTL6A regulates follicle-stimulating hormone-driven glycolysis in ovarian cancer cells via PGK1
ACTL6A regulates follicle-stimulating hormone-driven glycolysis in ovarian cancer cells via PGK1
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ACTL6A 通过 PGK1 调节卵巢癌细胞中促卵泡激素驱动的糖酵解
DOI：
10.1038/s41419-019-2050-y
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发表时间：
2019-10-24
影响因子：
9
通讯作者：
Wang, Qingying
中科院分区：
文献类型：
--
作者：
Zhang, Jiawen;Zhang, Jing;Wang, Qingying
糖酵解增强已被确定为癌症的标志。作为一种新的癌基因，ACTL 6A在几种类型的人类癌症中异常扩增，并已被证明可调节肿瘤的生长和进展。然而，ACTL 6A在卵巢癌的发生发展中的作用以及对癌症糖代谢的调节大多是未知的。在此，我们发现与邻近的非肿瘤组织相比，ACTL 6A在卵巢癌中过表达，并且ACTL 6A过表达与不良预后相关。ACTL 6A在体外的沉默抑制卵巢癌细胞的增殖、克隆生长和迁移，并降低葡萄糖利用、乳酸产生和丙酮酸水平。我们发现ACTL 6A和PGK 1在卵巢癌组织中的表达呈正相关。加强ACTL 6A的表达增加PGK 1的表达，而敲低ACTL 6A有相反的效果。ACTL 6A表达改变通过下调PGK 1抑制卵巢癌细胞体内致瘤性此外，ACTL 6A的表达受卵泡刺激素（FSH）刺激通过PI 3 K/AKT途径调节。重要的是，ACTL 6A调节卵巢癌中FSH增强的糖酵解。总之，我们的研究结果强调了ACTL 6A在卵巢癌发展中的关键作用，并确定了其对癌细胞葡萄糖代谢的贡献。
Enhanced glycolysis has been identified as a hallmark of cancer. As a novel oncogene, ACTL6A is aberrantly amplified in several types of human cancers and has been shown to regulate tumor growth and progression. However, the roles of ACTL6A in the development of ovarian cancer and the regulation of cancer glucose metabolism are mostly unknown. Here we show that ACTL6A is overexpressed in ovarian cancers compared with adjacent non-tumor tissues, and that ACTL6A overexpression correlates with poor prognosis. Silencing of ACTL6A in vitro inhibits proliferation, clonal growth, and migration, and decreases glucose utilization, lactate production, and pyruvate levels of ovarian cancer cells. We found a positive correlation between ACTL6A and PGK1 expression in ovarian cancer tissues. Enforced ACTL6A expression increased PGK1 expression, whereas knockdown of ACTL6A had the opposite effect. Altered ACTL6A expression inhibits the tumorigenicity of ovarian cancer cells in vivo by downregulating PGK1. In addition, the expression of ACTL6A is regulated by follicle-stimulating hormone (FSH) stimulation via PI3K/AKT pathway. Importantly, ACTL6A regulates FSH-enhanced glycolysis in ovarian cancer. Taken together, our findings highlight the critical role of ACTL6A in ovarian cancer development and identify its contribution to glucose metabolism of cancer cells.