PRL-3 improves colorectal cancer cell proliferation and invasion through IL-8 mediated glycolysis metabolism

PRL-3 improves colorectal cancer cell proliferation and invasion through IL-8 mediated glycolysis metabolism
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PRL-3 通过 IL-8 介导的糖酵解代谢改善结直肠癌细胞增殖和侵袭

DOI:
10.3892/ijo.2017.4090
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发表时间:
2017-10-01
影响因子:
5.2
通讯作者:
Chu, Zhonghua
Chu, Zhonghua
中科院分区:
医学2区
文献类型:
--
作者:
Xu, Heyang;Zeng, Yujie;Chu, Zhonghua

文献摘要

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再生肝-3磷酸酶(Phosphatase of regenerative liver-3, PRL-3)在结直肠癌肝转移灶中被发现过表达,而在原发肿瘤中很少表达,在结直肠癌细胞的转移中起重要作用。代谢重编程已被发现是癌细胞的一个标志,有氧糖酵解是癌细胞的一种代谢适应,促进细胞增殖。然而,PRL-3与结直肠癌细胞糖酵解之间的关系尚不清楚。在本研究中,我们探讨了PRL-3与糖酵解之间的关系。我们发现PRL-3可以改善结直肠癌细胞的葡萄糖假设、乳酸生成和降低细胞内ROS水平。此外,PRL-3提高了Glut1、HK2、PKM2和LDHA等糖酵解相关重要分子和酶的表达。此外,我们还探索了IL-8介导的PRL-3对糖酵解的增强作用。更重要的是,PRL-3通过改善糖酵解作用,显著增强结直肠癌细胞的增殖和侵袭能力。综上所述,这些结果提示PRL-3通过改善结直肠癌细胞中IL-8的分泌在糖酵解代谢中起重要作用,PRL-3介导的糖酵解促进了肿瘤转移。
Phosphatase of regenerating liver-3 (PRL-3) has been found to be overexpressed in liver metastases of colorectal cancer and rarely expressed in primary tumors, which plays an important role in the metastasis of colorectal cancer cells. Metabolism reprogramming has been found to be a hallmark of cancer cells, and aerobic glycolysis is a metabolic adaption for cancer cells and promotes cell proliferation. However, the association between PRL-3 and glycolysis in colorectal cancer cells is not well understood. In the present study, we explored the association between PRL-3 and glycolysis. We found that PRL-3 improved colorectal cancer cell glucose assumption, lactate production and reduced intracellular ROS levels. Besides, PRL-3 improved the expression of Glut1, HK2, PKM2 and LDHA, which are important glycolysis related molecules and enzymes. Moreover, we explored IL-8 mediated enhancement of glycolysis by PRL-3. More importantly, the proliferation and invasion of colorectal cancer cells were enhanced significantly by PRL-3 through improving glycolysis. Taken together, these results implicated the important role of PRL-3 in glycolysis metabolism through improving IL-8 secretion in colorectal cancer cells, and PRL-3 mediated glycolysis contributed to the promotion of cancer metastasis.