title: CD44 enhances the epithelial-mesenchymal transition in association with             colon cancer invasion.
abstract: The metastatic process involves the migration and invasion of cancer cells             throughout the body to produce secondary tumors at distant sites. Through of epithelial-mesenchymal             transition (EMT), cancer cells employ developmental processes to gain migratory             and invasive properties. CD44 is the transmembrane adhesion receptor for Hyaluronan             (HA) and plays a central role in the remodeling and degradation of HA that leads             to cell migration, as well as to cancer invasion and metastasis. CD44 is highly             expressed in primary and metastatic colon cancer but lowly expressed in normal             tissues. We evaluated the impact of CD44 on EMT and invasion of colon cancer cells.             The functional role of CD44 in EMT was determined by the overexpression or knockdown             of CD44. CD44 was overexpressed by transfection with plasmid-RT-PCR product and             knockdown of CD44 by small hairpin RNA (shRNA)-mediated depletion of CD44 in SW480             colon cancer cells. Morphological changes were evaluated by confocal laser microscopy             in the culture media. The expression of EMT markers (E-cadherin/N-cadherin/vimentin/fibronectin/actin/MMPs)             and CD44/EGFR/PI3K-Akt signaling were evaluated using western blotting. The influence             of EMT in tumor biology was assessed with proliferation, migration and invasion             assays. EMT changes increased in CD44-overexpressing SW480 cells and decreased             in CD44 knockdown cells. CD44 activation induced expression of EGFR and activation             of phosphatidylinositol 3' kinase (PI3K)/Akt and expression of glycogen synthase             kinase-3 β (GSK-3β). In terms of EMT markers, CD44 downregulated E-cadherin expression,             upregulated N-cadherin, α-actin, vimentin, fibronectin and MT1-MMP, and inhibited             the formation of the membrane-associated E-cadherin-β-catenin complex, which resulted             in cell invasion and migration.
authors.affiliation: Department of Surgery, Chonnam National University Hospital and                     Medical School, Gwangju, Republic of Korea.
authors.forename: Sang Hyuk
authors.initials: SH
authors.lastname: Cho
authors.forename: Yeon Sun
authors.initials: YS
authors.lastname: Park
authors.forename: Hun Jin
authors.initials: HJ
authors.lastname: Kim
authors.forename: Chang Hyun
authors.initials: CH
authors.lastname: Kim
authors.forename: Sang Woo
authors.initials: SW
authors.lastname: Lim
authors.forename: Jung Wook
authors.initials: JW
authors.lastname: Huh
authors.forename: Jae Hyuk
authors.initials: JH
authors.lastname: Lee
authors.forename: Hyeong Rok
authors.initials: HR
authors.lastname: Kim
mesh_terms: D000943:Antigens, Differentiation / Q000378:metabolism; D015820:Cadherins / Q000235:genetics / Q000378:metabolism; D018929:Cell Culture Techniques; D045744:Cell Line, Tumor; D002465:Cell Movement; D048430:Cell Shape; D003110:Colonic Neoplasms; D058750:Epithelial-Mesenchymal Transition; D066246:ErbB Receptors / Q000235:genetics / Q000378:metabolism; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D018960:Hyaluronan Receptors / Q000235:genetics / Q000378:metabolism*; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism; D053511:Matrix Metalloproteinase 14 / Q000378:metabolism; D015398:Signal Transduction; D014158:Transcription, Genetic; D015854:Up-Regulation; D014746:Vimentin / Q000378:metabolism; D051176:beta Catenin / Q000235:genetics / Q000378:metabolism
chemical_list: D000943:Antigens, Differentiation; C497483:CD44 protein, human; D015820:Cadherins; D018960:Hyaluronan Receptors; D047908:Intracellular Signaling Peptides and Proteins; D014746:Vimentin; D051176:beta Catenin; D066246:ErbB Receptors; C507086:MMP14 protein, human; D053511:Matrix Metalloproteinase 14