Limits...
SLC39A6: a potential target for diagnosis and therapy of esophageal carcinoma.

Cui XB, Shen YY, Jin TT, Li S, Li TT, Zhang SM, Peng H, Liu CX, Li SG, Yang L, Li N, Hu JM, Jiang JF, Li M, Liang WH, Li Y, Wei YT, Sun ZZ, Wu CY, Chen YZ, Li F - J Transl Med (2015)

Bottom Line: And the effects of SLC39A6 silencing by siRNA on cell proliferation, apoptosis, and invasiveness, as well as the proteins involved in epithelial-to-mesenchymal transition (EMT) of esophageal cancer cells, were studied.Increased expression of SLC39A6 was found to be closely correlated with histological grade and early Tumor-Node-Metastasis stage I/II.High tumorous SLC39A6 expression was significantly correlated with shorter overall survival (OS).

View Article: PubMed Central - PubMed

Affiliation: Department of Pathology and Key Laboratory for Xinjiang Endemic and Ethnic Diseases, Shihezi University School of Medicine, North 4th Road, 832002, Shihezi, China. cuixiaobin4363@foxmail.com.

ABSTRACT

Background: Esophageal squamous cell carcinoma (ESCC) is a highly lethal cancer, and its underlying molecular mechanisms are poorly understood. Recent large-scale genome-wide association studies in Chinese Han populations have identified an ESCC susceptibility locus within the SLC39A6 gene. Here, we sought to explore the expression and biological function of SLC39A6 in ESCC.

Methods: Multiethnic validation of SLC39A6 protein expression was performed in different cohorts of patients from Chinese Han and Kazakh populations in the Xinjiang region by immunohistochemistry. The associations among SLC39A6 expression, clinicopathological parameters, and prognosis outcomes of ESCC were analyzed. And the effects of SLC39A6 silencing by siRNA on cell proliferation, apoptosis, and invasiveness, as well as the proteins involved in epithelial-to-mesenchymal transition (EMT) of esophageal cancer cells, were studied.

Results: SLC39A6 protein expression increased progressively from normal esophageal epithelium (NEE) to low-grade intraepithelial neoplasia to ESCC, and finally reached the highest in high-grade intraepithelial neoplasia from Han ethnic. Similarly, SLC39A6 protein was significantly overexpressed in Kazakh ethnic ESCC compared with that in NEE. Increased expression of SLC39A6 was found to be closely correlated with histological grade and early Tumor-Node-Metastasis stage I/II. High tumorous SLC39A6 expression was significantly correlated with shorter overall survival (OS). Cox regression analysis confirmed that SLC39A6 expression was an independent prognostic factor for poor OS in ESCC. Experimentally, the suppression of SLC39A6 expression promoted ESCC cell apoptosis but abrogated proliferation and invasion, and induced an EMT phenotype that included enhanced expression of E-cadherin, loss of vimentin, and morphological changes in ESCC cells in vitro.

Conclusions: Combined, our findings highlight a tumor-promoting role for SLC39A6 in ESCC, suggesting that SLC39A6 could serve as an early detector of high-risk subjects and prognostic biomarker. The targeting of SLC39A6 might be a potential therapeutic strategy for blocking ESCC.

No MeSH data available.


Related in: MedlinePlus

SLC39A6 promotes the EMT phenotype and inhibition of SLC39A6 expression diminished invasion capacity of Eca109 and EC9706 cells. a SLC39A6-siRNA was transfected into Eca109 and EC9706 cells for 72 h and cells were harvested for an immunoblot analysis of vimentin and E-cadherin. Silencing SLC39A6 was accompanied by the increased expression of E-cadherin and loss of vimentin, which are all hallmarks of EMT markers. Knockdown of SLC39A6 results in morphological changes in Eca109 cell. b Photographs were taken using a Nikon microscope (phase contrast). Original magnification ×200. c Cell invasion assay was performed using Matrigel-coated transwell plates for Eca109 and EC9706 cells. Knockdown of SLC39A6 significantly reduced cell invasiveness in the two esophageal cancer cell lines compared with that in SLC39A6-siRNA controls. d The relative percentage of cells passing through a Matrigel filter (**p < 0.01). All experiments were performed at least three times with consistent and repeatable results
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

License 1 - License 2
getmorefigures.php?uid=PMC4595240&req=5

Fig6: SLC39A6 promotes the EMT phenotype and inhibition of SLC39A6 expression diminished invasion capacity of Eca109 and EC9706 cells. a SLC39A6-siRNA was transfected into Eca109 and EC9706 cells for 72 h and cells were harvested for an immunoblot analysis of vimentin and E-cadherin. Silencing SLC39A6 was accompanied by the increased expression of E-cadherin and loss of vimentin, which are all hallmarks of EMT markers. Knockdown of SLC39A6 results in morphological changes in Eca109 cell. b Photographs were taken using a Nikon microscope (phase contrast). Original magnification ×200. c Cell invasion assay was performed using Matrigel-coated transwell plates for Eca109 and EC9706 cells. Knockdown of SLC39A6 significantly reduced cell invasiveness in the two esophageal cancer cell lines compared with that in SLC39A6-siRNA controls. d The relative percentage of cells passing through a Matrigel filter (**p < 0.01). All experiments were performed at least three times with consistent and repeatable results

Mentions: Cancer metastasis is associated with EMT. To investigate whether SLC39A6 regulates EMT in esophageal cancer cells, the epithelial cell marker E-cadherin and mesenchymal marker vimentin were examined in Eca109 cell transfected with SLC39A6-siRNA and controls using the western blot. The epithelial marker E-cadherin was significantly upregulated, whereas the mesenchymal markers vimentin was significantly reduced in Eca109 cells with knockdown of SLC39A6 compared with the controls siRNA groups (Fig. 6a). In addition, cell morphology examination indicated that knockdown of SLC39A6 resulted in morphological changes in Eca109 cells (Fig. 6b).Fig. 6


SLC39A6: a potential target for diagnosis and therapy of esophageal carcinoma.

Cui XB, Shen YY, Jin TT, Li S, Li TT, Zhang SM, Peng H, Liu CX, Li SG, Yang L, Li N, Hu JM, Jiang JF, Li M, Liang WH, Li Y, Wei YT, Sun ZZ, Wu CY, Chen YZ, Li F - J Transl Med (2015)

SLC39A6 promotes the EMT phenotype and inhibition of SLC39A6 expression diminished invasion capacity of Eca109 and EC9706 cells. a SLC39A6-siRNA was transfected into Eca109 and EC9706 cells for 72 h and cells were harvested for an immunoblot analysis of vimentin and E-cadherin. Silencing SLC39A6 was accompanied by the increased expression of E-cadherin and loss of vimentin, which are all hallmarks of EMT markers. Knockdown of SLC39A6 results in morphological changes in Eca109 cell. b Photographs were taken using a Nikon microscope (phase contrast). Original magnification ×200. c Cell invasion assay was performed using Matrigel-coated transwell plates for Eca109 and EC9706 cells. Knockdown of SLC39A6 significantly reduced cell invasiveness in the two esophageal cancer cell lines compared with that in SLC39A6-siRNA controls. d The relative percentage of cells passing through a Matrigel filter (**p < 0.01). All experiments were performed at least three times with consistent and repeatable results
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4595240&req=5

Fig6: SLC39A6 promotes the EMT phenotype and inhibition of SLC39A6 expression diminished invasion capacity of Eca109 and EC9706 cells. a SLC39A6-siRNA was transfected into Eca109 and EC9706 cells for 72 h and cells were harvested for an immunoblot analysis of vimentin and E-cadherin. Silencing SLC39A6 was accompanied by the increased expression of E-cadherin and loss of vimentin, which are all hallmarks of EMT markers. Knockdown of SLC39A6 results in morphological changes in Eca109 cell. b Photographs were taken using a Nikon microscope (phase contrast). Original magnification ×200. c Cell invasion assay was performed using Matrigel-coated transwell plates for Eca109 and EC9706 cells. Knockdown of SLC39A6 significantly reduced cell invasiveness in the two esophageal cancer cell lines compared with that in SLC39A6-siRNA controls. d The relative percentage of cells passing through a Matrigel filter (**p < 0.01). All experiments were performed at least three times with consistent and repeatable results
Mentions: Cancer metastasis is associated with EMT. To investigate whether SLC39A6 regulates EMT in esophageal cancer cells, the epithelial cell marker E-cadherin and mesenchymal marker vimentin were examined in Eca109 cell transfected with SLC39A6-siRNA and controls using the western blot. The epithelial marker E-cadherin was significantly upregulated, whereas the mesenchymal markers vimentin was significantly reduced in Eca109 cells with knockdown of SLC39A6 compared with the controls siRNA groups (Fig. 6a). In addition, cell morphology examination indicated that knockdown of SLC39A6 resulted in morphological changes in Eca109 cells (Fig. 6b).Fig. 6

Bottom Line: And the effects of SLC39A6 silencing by siRNA on cell proliferation, apoptosis, and invasiveness, as well as the proteins involved in epithelial-to-mesenchymal transition (EMT) of esophageal cancer cells, were studied.Increased expression of SLC39A6 was found to be closely correlated with histological grade and early Tumor-Node-Metastasis stage I/II.High tumorous SLC39A6 expression was significantly correlated with shorter overall survival (OS).

View Article: PubMed Central - PubMed

Affiliation: Department of Pathology and Key Laboratory for Xinjiang Endemic and Ethnic Diseases, Shihezi University School of Medicine, North 4th Road, 832002, Shihezi, China. cuixiaobin4363@foxmail.com.

ABSTRACT

Background: Esophageal squamous cell carcinoma (ESCC) is a highly lethal cancer, and its underlying molecular mechanisms are poorly understood. Recent large-scale genome-wide association studies in Chinese Han populations have identified an ESCC susceptibility locus within the SLC39A6 gene. Here, we sought to explore the expression and biological function of SLC39A6 in ESCC.

Methods: Multiethnic validation of SLC39A6 protein expression was performed in different cohorts of patients from Chinese Han and Kazakh populations in the Xinjiang region by immunohistochemistry. The associations among SLC39A6 expression, clinicopathological parameters, and prognosis outcomes of ESCC were analyzed. And the effects of SLC39A6 silencing by siRNA on cell proliferation, apoptosis, and invasiveness, as well as the proteins involved in epithelial-to-mesenchymal transition (EMT) of esophageal cancer cells, were studied.

Results: SLC39A6 protein expression increased progressively from normal esophageal epithelium (NEE) to low-grade intraepithelial neoplasia to ESCC, and finally reached the highest in high-grade intraepithelial neoplasia from Han ethnic. Similarly, SLC39A6 protein was significantly overexpressed in Kazakh ethnic ESCC compared with that in NEE. Increased expression of SLC39A6 was found to be closely correlated with histological grade and early Tumor-Node-Metastasis stage I/II. High tumorous SLC39A6 expression was significantly correlated with shorter overall survival (OS). Cox regression analysis confirmed that SLC39A6 expression was an independent prognostic factor for poor OS in ESCC. Experimentally, the suppression of SLC39A6 expression promoted ESCC cell apoptosis but abrogated proliferation and invasion, and induced an EMT phenotype that included enhanced expression of E-cadherin, loss of vimentin, and morphological changes in ESCC cells in vitro.

Conclusions: Combined, our findings highlight a tumor-promoting role for SLC39A6 in ESCC, suggesting that SLC39A6 could serve as an early detector of high-risk subjects and prognostic biomarker. The targeting of SLC39A6 might be a potential therapeutic strategy for blocking ESCC.

No MeSH data available.


Related in: MedlinePlus