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乳酸支持细胞自主ECM的产生,以维持前列腺癌转移的行为

Luigi Ippolito¹, Assia Duatti², Marta Iozzo²

¹Department of Experimental and Clinical Biomedical Sciences, University of Florence, Viale Morgagni 50, 50134, Florence, Italy. luigi.ippolito@unifi.it.

|June 21, 2024

概括

与癌症相关的纤维细胞分泌乳酸,通过促进原蛋白的产生和信号传递,推动前列腺癌细胞的入侵. 抑制这种乳酸驱动的原路径可以减少癌细胞转移.

科学领域:

在瘤学瘤学.
癌症新陈代谢癌症新陈代谢
细胞外矩阵生物学细胞外矩阵生物学

背景情况:

富含细胞外基质 (ECM) 的瘤微环境促进癌细胞的入侵.
像乳酸盐这样的代谢物,特别是前列腺癌 (PCa) 中癌症相关纤维细胞 (CAF) 的代谢物,显著影响癌细胞行为.
CAFs贡献乳酸,影响PCa细胞中的代谢和转录过程.

研究的目的:

阐明CAF分泌的乳酸盐促进PCa细胞中的原基因表达的机制.
为了研究α-甲酸盐 (α-KG) 和原prolyl-4-hydroxylase (P4HA1) 在乳酸驱动的原合成中的作用.
为了确定通过迪斯科丁域受体1 (DDR1) 传递原蛋白信号对PCa细胞干细胞和侵入的影响.

主要方法:

分析CAF衍生乳酸受影响的PCa细胞中的代谢和转录调节.
研究乳酸对α-KG依赖的P4HA1的激活.
评估新合成的原和DDR1激活在PCa细胞入侵和转移中的作用.
评估抑制乳酸诱导的原氧化和DDR1激活对PCa细胞殖民的作用.

主要成果:

由CAF分泌的乳酸盐增强了PCa细胞对原基因的表达.
PCa细胞利用增加的α-KG来激活P4HA1,从而支持原氧化.
合成的原激活DDR1,促进干状和侵入性PCa细胞特征.
抑制原氧化和DDR1激活可以抑制PCa细胞转移殖民.

结论:

由CAF分泌的乳酸驱动PCa中的原蛋白生产和信号,增强入侵.
乳酸-α-KG-P4HA1-原-DDR1轴代表了PCa转移的新型营养驱动途径.
针对这种途径提供了一个潜在的治疗策略,以减少前列腺癌的进展.

关键词:

这些CAF是CAF.通过原体的氧化.原体的信号传递乳酸代谢乳酸代谢

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