Zhu Zhenyu, Zhang Xukui, Guo Hongliang, Fu Ling, Pan Ganlin, Sun Yinggang
Surgiaca Ward 4 (Colorectum & Intestinal Surgery), Shandong Tumor Hospital, Jinan, 250117, Shandong, China.
Mol Cell Biochem. 2015 Feb;400(1-2):287-95. doi: 10.1007/s11010-014-2285-y. Epub 2014 Dec 5.
CXCL13, an inflammatory factor in the microenvironment, plays a vital role in the progression of inflammatory diseases and tumors. CXCL13 and its receptor CXCR5 have been reported to be associated with poor prognosis of advanced colon cancer. However, the molecular mechanisms of CXCL13-CXCR5 axis in colon cancer remain elusive. The aim of this study was to investigate the role of CXCR5-CXCL13 axis in the growth and invasion of colon cancer cells. Our results showed that CXCL13 promoted the growth, migration, and matrigel invasion of colon cancer cells. Furthermore, CXCL13 increased the expression and secretion of MMP-13, and stimulated the activation of PI3K/AKT pathway. After knockdown of CXCR5 by siRNA, the biological functions of colon cancer cells regulated by CXCL13 were significantly inhibited. In addition, inhibition of PI3K/AKT pathway by specific inhibitor LY294002 suppressed the CXCL13-mediated growth, migration, and invasion of colon cancer cells. Together, our findings suggest that CXCL13-CXCR5 axis promotes the growth, migration, and invasion of colon cancer cells, probably via PI3K/AKT pathway. Thus, CXCL13 may be a useful biomarker for the detection and treatment of colon cancer.
CXCL13是微环境中的一种炎症因子，在炎症性疾病和肿瘤的进展中起着至关重要的作用。据报道，CXCL13及其受体CXCR5与晚期结肠癌的不良预后相关。然而，CXCL13 - CXCR5轴在结肠癌中的分子机制仍不清楚。本研究的目的是探讨CXCR5 - CXCL13轴在结肠癌细胞生长和侵袭中的作用。我们的结果表明，CXCL13促进结肠癌细胞的生长、迁移和基质胶侵袭。此外，CXCL13增加MMP - 13的表达和分泌，并刺激PI3K/AKT通路的激活。用siRNA敲低CXCR5后，CXCL13调节的结肠癌细胞的生物学功能受到显著抑制。此外，特异性抑制剂LY294002抑制PI3K/AKT通路可抑制CXCL13介导的结肠癌细胞的生长、迁移和侵袭。总之，我们的研究结果表明，CXCL13 - CXCR5轴可能通过PI3K/AKT通路促进结肠癌细胞的生长、迁移和侵袭。因此，CXCL13可能是结肠癌检测和治疗的一个有用的生物标志物。
