title: Deferoxamine enhances cell migration and invasion through promotion of HIF-1α expression and epithelial-mesenchymal transition in colorectal cancer.
abstract: Deferoxamine (DFX), a metal chelator, has been previously reported to induce hypoxia and hypoxia-inducible factor-1α (HIF-1α) expression. HIF-1α is a common inducer of epithelial-mesenchymal transition (EMT) in many solid tumors. However, the effect of DFX on cancer metastasis and the related mechanisms are not well established. In the present study, we aimed to ascertain whether DFX enhances EMT and cancer metastasis in colorectal cancer. After confirmation of DFX-inducing HIF-1α expression, we examined the effect of DFX on cell adhesion, migration and invasion abilities and found a positive effect on the above functions. Consequently, cell morphology, cell growth and expression of EMT markers were assessed in cells with or without DFX treatment. We found that cells exposed to DFX were more isolated. They were spindle-shaped and looked similar to fibroblast-like cells, accompanied by increased anchorage-independent growth. DFX-treated cells expressed E-cadherin and plakoglobin at a higher level, and vimentin and N-cadherin at a lower level, when compared with these levels in control cells. Furthermore, the expression of E-cadherin in the cell membrane was markedly decreased in DFX-treated cells. These results suggest that DFX promotes cancer migration and invasion via a process consistent with EMT in colorectal cancer.
authors.affiliation: Guangdong Provincial Key Laboratory of Gastroenterology, Department of Gastroenterology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong 510515, P.R. China.
authors.forename: Wenjing
authors.initials: W
authors.lastname: Zhang
authors.forename: Yao
authors.initials: Y
authors.lastname: Wu
authors.forename: Qingqing
authors.initials: Q
authors.lastname: Yan
authors.forename: Feng
authors.initials: F
authors.lastname: Ma
authors.forename: Xinpeng
authors.initials: X
authors.lastname: Shi
authors.forename: Yingying
authors.initials: Y
authors.lastname: Zhao
authors.forename: Ying
authors.initials: Y
authors.lastname: Peng
authors.forename: Jide
authors.initials: J
authors.lastname: Wang
authors.forename: Bo
authors.initials: B
authors.lastname: Jiang
mesh_terms: D015820:Cadherins / Q000096:biosynthesis; D002448:Cell Adhesion / Q000187:drug effects; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D015179:Colorectal Neoplasms / Q000473:pathology*; D003676:Deferoxamine / Q000494:pharmacology*; D058750:Epithelial-Mesenchymal Transition / Q000187:drug effects*; D005353:Fibronectins / Q000378:metabolism; D045325:HCT116 Cells; D019073:HT29 Cells; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000096:biosynthesis*; D009361:Neoplasm Invasiveness / Q000473:pathology; D009362:Neoplasm Metastasis; D017262:Siderophores / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects; D014746:Vimentin / Q000096:biosynthesis; D014945:Wound Healing / Q000187:drug effects; D051185:gamma Catenin / Q000096:biosynthesis
chemical_list: D015820:Cadherins; D005353:Fibronectins; C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D017262:Siderophores; D014746:Vimentin; D051185:gamma Catenin; D003676:Deferoxamine