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ShRNA-mediated knock-down of CXCL8 inhibits tumor growth in colorectal liver metastasis.

Authors: Kumar, Abhishek  Cherukumilli, Madhuri  Mahmoudpour, Seyed Hamidreza  Brand, Karsten  Bandapalli, Obul Reddy 
Citation: Kumar A, etal., Biochem Biophys Res Commun. 2018 Jun 7;500(3):731-737. doi: 10.1016/j.bbrc.2018.04.144. Epub 2018 Apr 23.
Pubmed: (View Article at PubMed) PMID:29679563
DOI: Full-text: DOI:10.1016/j.bbrc.2018.04.144

CXCL8 belongs to proinflammatory chemokines that are predominantly involved in neutrophil chemotaxis and degranulation. Several studies have suggested that secretion of CXCL8 from cancer cells have a profound effect on tumor microenvironment. In this study, in continuation to our previous work of understanding the global picture of invasion related genes in colorectal liver metastases, we clearly show an up-regulation of CXCL8 expression in the tumor cells at the invasion front as compared to the tumor cells in the inner parts of the tumor. Furthermore, ShRNA mediated down-regulation of CXCL8 resulted in inhibition of cell proliferation, viability and invasion in vitro and a near complete growth reduction of tumor in vivo. We showed that CXCL8 secreted by tumor cells at the invasion front were able to promote migration through angiogenesis by upregulating VEGFA and invasion via the AKT/GSK3β/β-catenin/MMP7 pathway by upregulating BCL-2 confirming the key role of CXCL8 during tumor progression.

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RGD Object Information
RGD ID: 26884358
Created: 2020-05-08
Species: All species
Last Modified: 2020-05-08
Status: ACTIVE



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RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.