title: Wnt/β-catenin pathway is required for epithelial to mesenchymal transition in CXCL12 over expressed breast cancer cells.
abstract: CXCL12 is positively associated with the metastasis and prognosis of various human malignancies. Cancer-associated fibroblasts (CAFs), the main cells secreting CXCL12, are capable of inducing epithelial to mesenchymal transition (EMT) of breast cancer cells. However, it has not been completely understood whether CXCL12 is involved in EMT of breast cancer cells and the underlying mechanisms. The present study aimed to investigate the effects of CXCL12 on the EMT and cancer stem cell (CSC)-like phenotypes formation by transfecting pEGFP-N1-CXCL12 plasmid into MCF-7 cells. Real time-PCR and Western blot analysis demonstrated the successful over expression of CXCL12 in MCF-7 cells. Cell counting kit-8 assay, wound healing assay and Transwell invasion analysis confirmed that over expression of CXCL12 significantly promoted the proliferation, migration and invasion in MCF-7 cells (P<0.05). In addition, ALDH activity was dramatically enhanced compared with parental (P<0.001), accompanied by the notably elevated mRNA and protein levels of OCT-4, Nanog, and SOX2 in CXCL12 overexpressed-MCF-7 cells (P<0.001). Furthermore, we observed the down regulation of E-cadherin and up regulation of vimentin, N-cadherin, and α-SMA in CXCL12 overexpressed-MCF-7 cells (P<0.01). Meanwhile, western blot and immunofluorescence assay showed that over expression of CXCL12 activated Wnt/β-catenin pathway to induce EMT of MCF-7 cells, as evidenced by the increased expression of E-cadherin after silencing β-catenin by siRNA interference (P<0.001). Collectively, our findings suggested that over expression of CXCL12 could trigger EMT by activating Wnt/β-catenin pathway and induce CSC-like phenotypes formation to promote the proliferation and metastasis in MCF-7. Hence, CXCL12 may become a promising candidate for breast cancer therapy.
authors.affiliation: Department of Medical Ultrasonics, Hongqi Hospital of Mudanjiang Medical University Mudanjiang, Heilongjiang 157011, People's Republic of China.
authors.forename: Shumei
authors.initials: S
authors.lastname: Shan
authors.affiliation: Key Laboratory of Cancer Prevention and Treatment of Heilongjiang Province, Mudanjiang Medical University Mudanjiang, Heilongjiang 157011, People's Republic of China.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Lv
authors.affiliation: Department of Medical Ultrasonics, Hongqi Hospital of Mudanjiang Medical University Mudanjiang, Heilongjiang 157011, People's Republic of China.
authors.forename: Yiling
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: Department of Medical Ultrasonics, Hongqi Hospital of Mudanjiang Medical University Mudanjiang, Heilongjiang 157011, People's Republic of China.
authors.forename: Chunfeng
authors.initials: C
authors.lastname: Liu
authors.affiliation: Department of Medical Ultrasonics, Hongqi Hospital of Mudanjiang Medical University Mudanjiang, Heilongjiang 157011, People's Republic of China.
authors.forename: Yingyan
authors.initials: Y
authors.lastname: Sun
authors.affiliation: Department of Medical Ultrasonics, Hongqi Hospital of Mudanjiang Medical University Mudanjiang, Heilongjiang 157011, People's Republic of China.
authors.forename: Kemin
authors.initials: K
authors.lastname: Xi
authors.affiliation: Department of Medical Ultrasonics, Hongqi Hospital of Mudanjiang Medical University Mudanjiang, Heilongjiang 157011, People's Republic of China.
authors.forename: Jiayi
authors.initials: J
authors.lastname: Xiao
authors.affiliation: Department of Medical Ultrasonics, Hongqi Hospital of Mudanjiang Medical University Mudanjiang, Heilongjiang 157011, People's Republic of China.
authors.forename: Caijuan
authors.initials: C
authors.lastname: Li
mesh_terms: D015153:Blotting, Western; D001943:Breast Neoplasms / Q000378:metabolism / Q000473:pathology*; D054377:Chemokine CXCL12 / Q000378:metabolism*; D058750:Epithelial-Mesenchymal Transition / Q000502:physiology*; D005260:Female; D005455:Fluorescent Antibody Technique; D055785:Gene Knockdown Techniques; D006801:Humans; D061986:MCF-7 Cells; D014411:Neoplastic Stem Cells / Q000378:metabolism* / Q000473:pathology; D034741:RNA, Small Interfering; D060888:Real-Time Polymerase Chain Reaction; D014162:Transfection; D060449:Wnt Signaling Pathway / Q000502:physiology*
chemical_list: C515255:CXCL12 protein, human; D054377:Chemokine CXCL12; D034741:RNA, Small Interfering
keywords: CXCL12; Wnt/β-catenin pathway; breast cancer; cancer stem cell-like phenotypes; epithelial to mesenchymal transition