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.jpg): Failed to open stream: No such file or directory in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 117 Int+J+Clin+Exp+Pathol
2015 ; 8
(10
): 12357-67
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Wnt/?-catenin pathway is required for epithelial to mesenchymal transition in
CXCL12 over expressed breast cancer cells
#MMPMID26722422
Shan S
; Lv Q
; Zhao Y
; Liu C
; Sun Y
; Xi K
; Xiao J
; Li C
Int J Clin Exp Pathol
2015[]; 8
(10
): 12357-67
PMID26722422
show ga
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 ?-SMA in
CXCL12 overexpressed-MCF-7 cells (P<0.01). Meanwhile, western blot and
immunofluorescence assay showed that over expression of CXCL12 activated
Wnt/?-catenin pathway to induce EMT of MCF-7 cells, as evidenced by the increased
expression of E-cadherin after silencing ?-catenin by siRNA interference
(P<0.001). Collectively, our findings suggested that over expression of CXCL12
could trigger EMT by activating Wnt/?-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.