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Archive > Volume 26 Issue 6 > 2019,26(6):650-655. DOI:10.3872/j.issn.1007-385X.2019.06.006 Prev Next
Basic Research
AKT/MMP3 activation, not EMT pathway, participates in CCL20-induced invasion and migration of colon cancer SW480 cells
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Abstract:
[Abstract] Objective: To investigate the molecular mechanism of chemokine CCL20/CCR6 in promoting invasion and migration of colon cancer SW480 cells. Methods: Colorectal cancer SW480 cells with high expression of CCR6 receptor were screened by immunochemistry (IHC). After co-culture with recombinant human CCL20, the invasion and migration of SW480 cells were detected by Transwell assay and Wound-Healing assay, respectively. Expressions of EMT markers, AKT signal protein and target protein MMP3 were detected by immunofluorescence (IF) and WB. AKT signaling pathway as the key mechanism was confirmed by MK2206 blocking assay.The expressions of CCL20 and MMP3 in colorectal cancer tissues as well as their correlation were analyzed by TCGA database resources (https://portal.gdc.cancer.gov/). Results: CCL20 promoted the invasion and migration ability of SW480 cells significantly (all P <0.01), and this was induced by activation of AKT signaling and up-regulation of downstream target protein MMP3, instead of EMT.Blocking AKT signaling could significantly inhibit the invasion and migration of SW480 cells, and down-regulate MMP3 expression (P<0.05). TCGA platform data showed that the expressions of CCL20 and MMP3 in colorectal cancer tissues were significantly higher than those in normal mucosa tissues (P<0.05 or P<0.01), and an evidently positive correlation was found between CCL20 and MMP3 (r=0.051, P<0.01). Conclusion: The chemokine CCL20 promotes the invasion and migration of SW480 cells through AKT/MMP3 signal axis, but not the EMT.
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Project Supported:
Project supported by the National Natural Science Foundation of China (No. 81560472), Department of Health-Kunming Medical University Joint Project of Yunnan Province (No. 2017FE468 [-076]),Department of Science and Technology Key Fundation of Yunnan Province (No. 2018FA040), and the Funds for the Construction of Key Clinical Specialties of Colorectal Cancer in Yunnan Province (No. 2016-0137)
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