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Up-regulation of S100A16 expression promotes epithelial-mesenchymal transition via Notch1 pathway in breast cancer.

Zhou W, Pan H, Xia T, Xue J, Cheng L, Fan P, Zhang Y, Zhu W, Xue Y, Liu X, Ding Q, Liu Y, Wang S - J. Biomed. Sci. (2014)

Bottom Line: One major mechanistic change was that S100A16 was able to up-regulate the transcription factors Notch1, ZEB1, and ZEB2, which had the capacities to directly repress the expression of epithelial markers E-cadherin and β-catenin but increase mesenchymal markers N-cadherin and vimentin, a characterized phenotype of epithelial-mensenchymal transition (EMT).In addition to display with morphologic change, migration and invasion were increased in S100A16 over-expressed MCF-7 cells.Importantly, knockdown of Notch1 by specific siRNA could reverse the EMT induced by S100A16 overexpression, which confirmed that Notch1 played a critical role in the process of EMT induced by S100A16.

View Article: PubMed Central - PubMed

Affiliation: Department of Breast Surgery, The First Affiliated Hospital with Nanjing Medical University, 300 Guangzhou Road, 210029, Nanjing, China. zhouwenbin@njmu.edu.cn.

ABSTRACT

Background: Our previous studies demonstrated that S100A16 promotes adipogenesis and is involved in weight gain attenuation induced by dietary calcium. Till now, the function of S100A16 in the breast cancer remains to be elucidated.

Results: In this study, we observed that S100A16 was expressed in higher levels in human breast cancer tissues compared with paired adjacent non-cancerous tissues. Further examination showed that overexpression of S100A16 in MCF-7 cells could increase cell proliferation and colony formation. One major mechanistic change was that S100A16 was able to up-regulate the transcription factors Notch1, ZEB1, and ZEB2, which had the capacities to directly repress the expression of epithelial markers E-cadherin and β-catenin but increase mesenchymal markers N-cadherin and vimentin, a characterized phenotype of epithelial-mensenchymal transition (EMT). In addition to display with morphologic change, migration and invasion were increased in S100A16 over-expressed MCF-7 cells. Importantly, knockdown of Notch1 by specific siRNA could reverse the EMT induced by S100A16 overexpression, which confirmed that Notch1 played a critical role in the process of EMT induced by S100A16.

Conclusions: All together, our data indicated that S100A16 had a potential function to regulate some embryonic transcription factors to promote EMT in breast cancer cells which may be an important target site for the therapy of breast cancer.

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Related in: MedlinePlus

Up-regulation of S100A16 increased the capacities of proliferation, migration and invasion in MCF-7 cells. (A) S100A16 was transfected in MCF-7 cells. Western blot was used to measure S100A16 protein expression in control cells (MCF7-GFP) and S100A16 overexpression cells (MCF7-S100A16). (B) MTT assay showed that the cell proliferation rate was increased after S100A16 overexpression in MCF-7 cells (Bars, mean ± SD, *P < 0.05, **P < 0.01). (C) Colony formation assay confirmed that up-regulation of S100A16 markedly increased the number of cell colonies in MCF-7 cells (P < 0.05). (D, E) Transwell migration and invasion assays showed that up-regulation of S100A16 increased cell migration (D) and invasion (E) abilities compared with control cells (P < 0.05). Triplicate assays were used for each experiment (Magnification, 10×).
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Fig2: Up-regulation of S100A16 increased the capacities of proliferation, migration and invasion in MCF-7 cells. (A) S100A16 was transfected in MCF-7 cells. Western blot was used to measure S100A16 protein expression in control cells (MCF7-GFP) and S100A16 overexpression cells (MCF7-S100A16). (B) MTT assay showed that the cell proliferation rate was increased after S100A16 overexpression in MCF-7 cells (Bars, mean ± SD, *P < 0.05, **P < 0.01). (C) Colony formation assay confirmed that up-regulation of S100A16 markedly increased the number of cell colonies in MCF-7 cells (P < 0.05). (D, E) Transwell migration and invasion assays showed that up-regulation of S100A16 increased cell migration (D) and invasion (E) abilities compared with control cells (P < 0.05). Triplicate assays were used for each experiment (Magnification, 10×).

Mentions: The results of clinical samples indicated that S100A16 may be associated with aggressive behavior in breast cancer (Figure 1A and B). To validate this, we overexpressed S100A16 using pLV-S100A16 lentivirus in MCF-7 and T47D cells. The protein levels of S100A16 were elevated after infection with pLV-S100A16 lentivirus (Figure 2A and Additional file 1: Figure S2). The new cell lines were named as MCF7-S100A16 and T47D-S100A16, and the control cell lines were named as MCF7-GFP and T47D-GFP.Figure 2


Up-regulation of S100A16 expression promotes epithelial-mesenchymal transition via Notch1 pathway in breast cancer.

Zhou W, Pan H, Xia T, Xue J, Cheng L, Fan P, Zhang Y, Zhu W, Xue Y, Liu X, Ding Q, Liu Y, Wang S - J. Biomed. Sci. (2014)

Up-regulation of S100A16 increased the capacities of proliferation, migration and invasion in MCF-7 cells. (A) S100A16 was transfected in MCF-7 cells. Western blot was used to measure S100A16 protein expression in control cells (MCF7-GFP) and S100A16 overexpression cells (MCF7-S100A16). (B) MTT assay showed that the cell proliferation rate was increased after S100A16 overexpression in MCF-7 cells (Bars, mean ± SD, *P < 0.05, **P < 0.01). (C) Colony formation assay confirmed that up-regulation of S100A16 markedly increased the number of cell colonies in MCF-7 cells (P < 0.05). (D, E) Transwell migration and invasion assays showed that up-regulation of S100A16 increased cell migration (D) and invasion (E) abilities compared with control cells (P < 0.05). Triplicate assays were used for each experiment (Magnification, 10×).
© Copyright Policy - open-access
Related In: Results  -  Collection

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Show All Figures
getmorefigures.php?uid=PMC4197258&req=5

Fig2: Up-regulation of S100A16 increased the capacities of proliferation, migration and invasion in MCF-7 cells. (A) S100A16 was transfected in MCF-7 cells. Western blot was used to measure S100A16 protein expression in control cells (MCF7-GFP) and S100A16 overexpression cells (MCF7-S100A16). (B) MTT assay showed that the cell proliferation rate was increased after S100A16 overexpression in MCF-7 cells (Bars, mean ± SD, *P < 0.05, **P < 0.01). (C) Colony formation assay confirmed that up-regulation of S100A16 markedly increased the number of cell colonies in MCF-7 cells (P < 0.05). (D, E) Transwell migration and invasion assays showed that up-regulation of S100A16 increased cell migration (D) and invasion (E) abilities compared with control cells (P < 0.05). Triplicate assays were used for each experiment (Magnification, 10×).
Mentions: The results of clinical samples indicated that S100A16 may be associated with aggressive behavior in breast cancer (Figure 1A and B). To validate this, we overexpressed S100A16 using pLV-S100A16 lentivirus in MCF-7 and T47D cells. The protein levels of S100A16 were elevated after infection with pLV-S100A16 lentivirus (Figure 2A and Additional file 1: Figure S2). The new cell lines were named as MCF7-S100A16 and T47D-S100A16, and the control cell lines were named as MCF7-GFP and T47D-GFP.Figure 2

Bottom Line: One major mechanistic change was that S100A16 was able to up-regulate the transcription factors Notch1, ZEB1, and ZEB2, which had the capacities to directly repress the expression of epithelial markers E-cadherin and β-catenin but increase mesenchymal markers N-cadherin and vimentin, a characterized phenotype of epithelial-mensenchymal transition (EMT).In addition to display with morphologic change, migration and invasion were increased in S100A16 over-expressed MCF-7 cells.Importantly, knockdown of Notch1 by specific siRNA could reverse the EMT induced by S100A16 overexpression, which confirmed that Notch1 played a critical role in the process of EMT induced by S100A16.

View Article: PubMed Central - PubMed

Affiliation: Department of Breast Surgery, The First Affiliated Hospital with Nanjing Medical University, 300 Guangzhou Road, 210029, Nanjing, China. zhouwenbin@njmu.edu.cn.

ABSTRACT

Background: Our previous studies demonstrated that S100A16 promotes adipogenesis and is involved in weight gain attenuation induced by dietary calcium. Till now, the function of S100A16 in the breast cancer remains to be elucidated.

Results: In this study, we observed that S100A16 was expressed in higher levels in human breast cancer tissues compared with paired adjacent non-cancerous tissues. Further examination showed that overexpression of S100A16 in MCF-7 cells could increase cell proliferation and colony formation. One major mechanistic change was that S100A16 was able to up-regulate the transcription factors Notch1, ZEB1, and ZEB2, which had the capacities to directly repress the expression of epithelial markers E-cadherin and β-catenin but increase mesenchymal markers N-cadherin and vimentin, a characterized phenotype of epithelial-mensenchymal transition (EMT). In addition to display with morphologic change, migration and invasion were increased in S100A16 over-expressed MCF-7 cells. Importantly, knockdown of Notch1 by specific siRNA could reverse the EMT induced by S100A16 overexpression, which confirmed that Notch1 played a critical role in the process of EMT induced by S100A16.

Conclusions: All together, our data indicated that S100A16 had a potential function to regulate some embryonic transcription factors to promote EMT in breast cancer cells which may be an important target site for the therapy of breast cancer.

Show MeSH
Related in: MedlinePlus