6533b7dafe1ef96bd126f5cd
RESEARCH PRODUCT
ShRNA-mediated knock-down of CXCL8 inhibits tumor growth in colorectal liver metastasis.
Seyed Hamidreza MahmoudpourAbhishek KumarKarsten BrandMadhuri CherukumilliObul Reddy Bandapallisubject
musculoskeletal diseases0301 basic medicineAngiogenesisCell SurvivalBiophysicsDown-RegulationApoptosisBiologyBiochemistryProinflammatory cytokineMetastasis03 medical and health sciencesMice0302 clinical medicineCell Line TumormedicineAnimalsHumansNeoplasm InvasivenessAmino Acid SequenceRNA MessengerRNA Small InterferingMolecular BiologyProtein kinase BConserved SequenceCell ProliferationTumor microenvironmentInterleukin-8Liver NeoplasmsCell Biologymedicine.diseaseXenograft Model Antitumor AssaysUp-RegulationGene Expression Regulation NeoplasticVascular endothelial growth factor A030104 developmental biologyTumor progression030220 oncology & carcinogenesisGene Knockdown TechniquesCancer cellCancer researchColorectal Neoplasmsdescription
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.
| year | journal | country | edition | language |
|---|---|---|---|---|
| 2018-06-01 | Biochemical and biophysical research communications |