向SOX4/PCK2信号抑制神经内分泌转基因差异化割耐性前列腺癌的抑制
Nan Jing1,2, Zhenkeke Tao1, Xinxing Du3
1State Key Laboratory of Systems Medicine for Cancer, Renji-Med-X Stem Cell Research Center, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200127, China.
Biology direct
|July 16, 2024
概括
SOX4通过激活PCK2和碳水化合物代谢来促进神经内分泌前列腺癌 (NEPC). 准SOX4/PCK2通路可能会阻断前列腺癌中NE转差异化.
科学领域:
- 在瘤学瘤学.
- 分子生物学分子生物学
- 代谢过程中的代谢.
背景情况:
- 神经内分泌前列腺癌 (NEPC) 是前列腺癌 (PCa) 的致命亚型.
- NEPC的特点是受体 (AR) 信号损失和对AR向疗法的抵抗.
- 第二代AR阻塞剂可以诱导NE转差异化,导致NEPC,但机制尚不清楚.
研究的目的:
- 阐明在前列腺癌中NE转差异化背后的分子机制.
- 确定参与向NEPC过渡的关键监管机构.
- 探索NEPC的潜在治疗点.
主要方法:
- 选公共数据集以确定候选基因,重点关注SOX4.
- 在临床组织中验证了SOX4表达,并评估了它在前列腺癌细胞系 (体外) 和异种移植 (体内) 中的作用.
- 利用RNA-seq,ATAC-seq,代谢学和生物化学分析来确定SOX4作用的机制.
主要成果:
- 在NEPC中,SOX4表达显著升高,并促进恶性表型,如增殖和迁移.
- SOX4的过度表达抑制AR的表达,并提高NE标记基因的调节,而SOX4的淘汰会逆转这些效应.
- SOX4直接准PCK2,激活碳水化合物代谢,并通过SOX4/PCK2通路促进NE转分化.
结论:
- 在前列腺癌中,SOX4通过SOX4/PCK2途径通过激活碳水化合物代谢来驱动NE转差.
- SOX4/PCK2通路代表了抑制前列腺癌中NE转分化的新疗法标.
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