Rac1通过上调SOX9促进糖代谢重编程和结肠癌细胞生长,Cancer Science

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Rac1通过上调SOX9促进糖代谢重编程和结肠癌细胞生长
Cancer Science ( IF 4.5 ) Pub Date : 2022-11-12 , DOI: 10.1111/cas.15652
Jiaxin Liang ₁ , Qiang Liu ₁ , Longzheng Xia ₁ , Jinguan Lin ₁ , Linda Oyang ₁ , Shiming Tan ₁ , Qiu Peng ₁ , Xianjie Jiang ₁ , Xuemeng Xu ₁ , Nayiyuan Wu ₁ , Yanyan Tang ₁ , Min Su ₁ , Xia Luo ₁ , Yiqing Yang ₁ , Qianjin Liao _{1,

2} , Yujuan Zhou _{1,

2}

Affiliation

代谢重编程是肿瘤细胞的生存法则，肿瘤细胞可以通过改变能量代谢方式来满足其高代谢需求。肿瘤细胞的代谢重编程是肿瘤恶性表型的重要生化基础。Ras相关的C3肉毒杆菌毒素底物1（Rac1）在多种肿瘤中异常表达，在肿瘤细胞的增殖、侵袭和迁移中起重要作用。然而，Rac1 在肿瘤代谢重编程中的作用仍不清楚。在此，我们发现 Rac1 在结肠癌组织和细胞系中高表达。Rac1通过上调SOX9促进结肠癌细胞的增殖、迁移和侵袭，SOX9作为转录因子可直接与HK2和G6PD的启动子结合基因并调节它们的转录活性。Rac1 通过 PI3K/AKT 信号通路上调 SOX9 的表达。此外，Rac1 可通过介导 SOX9/HK2/G6PD 轴促进结肠癌细胞的糖酵解和磷酸戊糖通路的激活。这些发现揭示了涉及 Rac1/SOX9/HK2/G6PD 在结肠癌发生和发展过程中的新调控轴，提供了新的有希望的治疗靶点。

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Rac1 promotes the reprogramming of glucose metabolism and the growth of colon cancer cells through upregulating SOX9

Metabolic reprogramming is the survival rule of tumor cells, and tumor cells can meet their high metabolic requirements by changing the energy metabolism mode. Metabolic reprogramming of tumor cells is an important biochemical basis of tumor malignant phenotypes. Ras-related C3 botulinum toxin substrate 1 (Rac1) is abnormally expressed in a variety of tumors and plays an important role in the proliferation, invasion, and migration of tumor cells. However, the role of Rac1 in tumor metabolic reprogramming is still unclear. Herein, we revealed that Rac1 was highly expressed in colon cancer tissues and cell lines. Rac1 promotes the proliferation, migration, and invasion of colon cancer cells by upregulating SOX9, which as a transcription factor can directly bind to the promoters of HK2 and G6PD genes and regulate their transcriptional activity. Rac1 upregulates the expression of SOX9 through the PI3K/AKT signaling pathway. Moreover, Rac1 can promote glycolysis and the activation of the pentose phosphate pathway in colon cancer cells by mediating the axis of SOX9/HK2/G6PD. These findings reveal novel regulatory axes involving Rac1/SOX9/HK2/G6PD in the development and progression of colon cancer, providing novel promising therapeutic targets.

更新日期：2022-11-12

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