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The axis of CXCR4/SDF-1 plays a role in colon cancer cell adhesion through regulation of the AKT and IGF1R signalling pathways

Zheng, Fei, Zhang, Zhongtao, Flamini, Valentina, Jiang, Wen and Cui, Yuxin 2017. The axis of CXCR4/SDF-1 plays a role in colon cancer cell adhesion through regulation of the AKT and IGF1R signalling pathways. Anticancer Research 37 (8) , pp. 4361-4369. 10.21873/anticanres.11830

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Abstract

Background/aim: Colorectal cancer (CRC) is the third most common cancer in the world. The high mortality of this tumor is mainly due to its invasive properties, as it forms metastases in multiple organs, preferentially in the liver. There has evidence showing that C-X-C chemokine receptor type 4 (CXCR-4) and its ligand, stromal cell-derived factor-1 (SDF-1), plays an important role in cancer progression and metastasis. However, the molecular mechanism underling the CRCR4-mediated CRC metastasis has not been well characterized. In this study, we aimed to investigate the roles of CXCR4 in colorectal cancer using the clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9 (Cas9)-based genomic editing technique. Materials and methods: We knocked-down CXCR4 using specific guide-RNA linked CRISPR/Cas9 in HT115 and COLO201 colon cancer cell lines which exhibited high levels of endogenous CXCR4 gene expression. Stable HT115 cells with CXCR4 knock-down were established by CRISPR plasmid transfection and validation was confirmed using T7 endonuclease 1 (T7EN1), flow cytometry (FACS) and western blotting assays. Results: Knock-down of CXCR4 did not decrease proliferation of HT115 cells, but decreased the adhesion potential of cells to the human umbilical vein endothelial cells (HUVEC) and extracellular matrix. We further demonstrated that the AKT and type 1 insulin-like growth factor receptor (IGF1R) signalling pathways may be involved in the alteration of adhesion in CRC cells when CXCR4 is knocked down. Conclusion: Our data suggest that CXCR4 plays a key role in colorectal cancer progression via the mediation of tumor cell adhesion. The Axis of CXCR4/SDF-1 Plays a Role in Colon Cancer Cell Adhesion Through... | Request PDF. Available from: https://www.researchgate.net/publication/319179295_The_Axis_of_CXCR4SDF-1_Plays_a_Role_in_Colon_Cancer_Cell_Adhesion_Through_Regulation_of_the_AKT_and_IGF1R_Signalling_Pathways [accessed Jan 08 2018].

Item Type: Article
Date Type: Publication
Status: Published
Schools: Medicine
Publisher: International Institute of Anticancer Research
ISSN: 0250-7005
Date of First Compliant Deposit: 15 January 2018
Date of Acceptance: 7 June 2017
Last Modified: 22 Jan 2018 12:22
URI: http://orca.cf.ac.uk/id/eprint/107907

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