Branched-Chain Amino Acid Catabolism Promotes Ovarian Cancer Cell Proliferation via Phosphorylation of mTOR.

IF 2 Q3 ONCOLOGY
Hannah J Lusk, Monica A Haughan, Tova M Bergsten, Joanna E Burdette, Laura M Sanchez
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Abstract

Significance: This study uncovers altered amino acid metabolism, specifically increased BCAA catabolism, at the interface of ovarian cancer cells and omental tissue in a coculture model of HGSOC secondary metastasis. Enhanced BCAA catabolism promotes cancer cell proliferation through mTOR signaling, presenting potential therapeutic value. These findings deepen our understanding of HGSOC pathogenesis and the metastatic tumor microenvironment, offering insights for developing new treatment strategies.

支链氨基酸分解代谢通过磷酸化mTOR促进卵巢癌细胞增殖。
卵巢癌是卵巢患者癌症相关死亡的第六大原因,而高级别浆液性卵巢癌(HGSOC)是最常见和最致命的亚型。HGSOC具有明显的侵袭性转移模式,可起源于输卵管,伴输卵管上皮细胞(FTE)的转化,转移到卵巢,随后转移到网膜和腹膜腔。大网膜是一个特殊的转移部位,大网膜转移的代谢交换可能提供酶或受体靶点来阻止转移。在这项研究中,我们采用了质谱成像(MSI)方案来研究在小鼠网膜外植体附近生长的致瘤性FTE细胞的三维共培养的空间位置,作为早期转移定植的模型。我们的分析揭示了致瘤性FTE/网膜共培养中几种代谢物的改变,即支链氨基酸(BCAA)的变化,包括缬氨酸。我们使用LC-MS测定了大网膜共培养中缬氨酸、其他支链氨基酸和其他氨基酸衍生代谢物的高消耗。我们的分析显示,当使用活培养系统中细胞培养基的MSI监测代谢物浓度时,值得注意的是,MSI数据如何产生诱导电离抑制的特征。缬氨酸的补充增强了致瘤性FTE细胞的增殖和mTOR信号,表明BCAA可能是肿瘤细胞在大网膜定植过程中利用的一种营养物质,也可能是转移的靶点。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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