Nuclear transcription factor CDX2 inhibits gastric cancer-cell growth and reverses epithelial-to-mesenchymal transition in vitro and in vivo

Zhang, Jianfeng; Qu, Lei; Qian, Xue‐Fen; Xia, Beilei; Mao, Zhen-biao; Chen, Weichang

doi:10.3892/mmr.2015.4114

Cited by 23 publications

(18 citation statements)

References 38 publications

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“…However, another study showed that CDX2 overexpression suppressed cell migration and invasion in MGC-803 cells and that CDX2 silencing promoted migration and invasion in NCI-N87 cells [33], indicating that CDX2 may inhibit migration and invasion of gastric cancer cells. Moreover, another report showed that ectopic expression of CDX2 reduced migration and invasion in MKN-45 cells [36], which is contrary to our ndings in MKN-45 cells. The inconsistency in these results may be due to the different gastric cancer cell lines used in the studies.…”

Section: Discussioncontrasting

confidence: 99%

CDX2 and Reg IV Expression and Correlation in Gastric Cancer

Chai

Hui-fen

et al. 2020

Preprint

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Background: Ectopic expression of CDX2 is associated with the development and progression of gastric cancer. Previous studies showed that CDX2 may be an upstream regulator of Reg IV expression in gastric cancer, and our previous report showed that Reg IV upregulated SOX9 expression and enhanced cell migration and invasion in gastric cancer cells. However, the regulatory roles of CDX2 have not been clarified in gastric cancer, and the correlation between CDX2 and Reg IV requires further study.Methods: CDX2 and Reg IV were examined in gastric cancer specimens and paired adjacent tissues via real-time PCR and immunohistochemistry (IHC). The association between CDX2 and Reg IV was assessed using the χ2-test and Spearman’s rank correlation. To verify their relationship, knockdown and exogenous expression of CDX2 or Reg IV were performed in AGS and MKN-45 gastric cancer cells, and their expression was subsequently analyzed via a real-time PCR and western blotting. Wound-healing and Transwell assays were used to examine migration and invasion in AGS and MKN-45 cells following CDX2 silencing or overexpression.Results: A positive correlation was observed between CDX2 and Reg IV expression at the mRNA and protein levels in gastric cancer tissues. CDX2 silencing significantly downregulated Reg IV expression, and CDX2 overexpression significantly upregulated Reg IV expression in AGS and MKN-45 cells. Neither Reg IV silencing nor overexpression had any effect on CDX2 protein expression in AGS or MKN-45 cells, even though both affected the expression of CDX2 mRNA. Functionally, CDX2 silencing significantly inhibited cell migration and invasion, and CDX2 overexpression significantly promoted cell migration and invasion in AGS and MKN-45 cells.Conclusions: Our findings demonstrate that CDX2 expression was positively correlated with that of Reg IV in gastric cancer, and CDX2 promoted cell migration and invasion through upregulation of Reg IV expression in gastric cancer cells.

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Section: Discussioncontrasting

confidence: 99%

CDX2 and Reg IV Expression and Correlation in Gastric Cancer

Chai

Hui-fen

et al. 2020

Preprint

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“…However, it is ectopically expressed in IM lesions of the stomach and intestinal-type gastric carcinoma [1][2][3][4][5][6][7][8]. Several studies have reported that CDX2 acts as a tumor suppressor in gastric cancer [6][7][8][21][22][23][24][25][26][27][28][29][30][31]. However, others consider CDX2 an oncogene in gastric cancer [1,2,[9][10][11][12][13][14][15][16][17][18][19][20].…”

Section: Discussionmentioning

confidence: 99%

CDX2 and Reg IV expression and correlation in gastric cancer

Chai

Hui-fen

et al. 2020

Preprint

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Background: Ectopic expression of CDX2 is associated with the development and progression of gastric cancer. Previous studies showed that CDX2 may be an upstream regulator of Reg IV expression in gastric cancer, and our previous report showed that Reg IV upregulated SOX9 expression and enhanced cell migration and invasion in gastric cancer cells. However, the regulatory roles of CDX2 have not been clarified in gastric cancer, and the correlation between CDX2 and Reg IV requires further study. Methods: CDX2 and Reg IV were examined in gastric cancer specimens and paired adjacent tissues via real-time PCR and immunohistochemistry (IHC). The association between CDX2 and Reg IV was assessed using the χ 2 -test and Spearman’s rank correlation. To verify their relationship, knockdown and exogenous expression of CDX2 or Reg IV were performed in AGS and MKN-45 gastric cancer cells, and their expression was subsequently analyzed via a real-time PCR and western blotting. Wound-healing and Transwell assays were used to examine migration and invasion in AGS and MKN-45 cells following CDX2 silencing or overexpression. Results: A positive correlation was observed between CDX2 and Reg IV expression at the mRNA and protein levels in gastric cancer tissues. CDX2 silencing significantly downregulated Reg IV expression, and CDX2 overexpression significantly upregulated Reg IV expression in AGS and MKN-45 cells. Neither Reg IV silencing nor overexpression had any effect on CDX2 protein expression in AGS or MKN-45 cells, even though both affected the expression of CDX2 mRNA. Functionally, CDX2 silencing significantly inhibited cell migration and invasion, and CDX2 overexpression significantly promoted cell migration and invasion in AGS and MKN-45 cells. Conclusions: Our findings demonstrate that CDX2 expression was positively correlated with that of Reg IV in gastric cancer, and CDX2 promoted cell migration and invasion through upregulation of Reg IV expression in AGS and MKN-45 cells.

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“…It was previously reported that the CDX2 gene promoter was highly methylated in human MKN45 gastric cancer cell line, and the expression levels of CDX2 mRNA were extremely low and CDX2 protein was not expressed. After incubation with three levels of 5-aza-CdR (inhibitor of methylation) for 72 h, the expression levels of CDX2 mRNA and protein were upregulated in MKN45 cells ( 11 ). However, it was reported that the expression of CDX2 gene was related to post-transcriptional regulation, such as the phosphorylation of CDX2 protein, rather than epigenetic modification (DNA methylation, histone acetylation) ( 12 ).…”

Section: Discussionmentioning

confidence: 99%

Methylation of CDX2 gene promoter in the prediction of treatment efficacy in colorectal cancer

Wang

et al. 2018

Oncol Lett

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The aim of the present study was to examine the diagnosis of methylation of CDX2 gene promoter in colorectal cancer (CRC) and assessed its value in the prediction of treatment efficacy. Sixty patients who were diagnosed as CRCs for the first time, 60 patients with hyperplastic polyps (HPs) and adenomas, and 60 patients with inflammatory lesions or healthy patients (control group) were included in the present study. The methylation levels of CDX2 gene promoter were detected by methylation-specific polymerase chain reaction (MSP), and the expression levels of CDX2 mRNA were detected by fluorescence quantitative PCR. Treatment options, such as surgery, radiotherapy and chemotherapy, were chosen on the basis of TNM staging of CRC patients. The tumor-free survival, relapse rate and mortality were also recorded. The methylation rate was 71.67% (43/60) and significantly higher in the CRC group as compared to the HP/adenoma and control groups, P<0.05. Moreover, they showed further increase with higher degree of TNM staging. The expression levels of CDX2 mRNA was significantly lower in the CRC group in comparison to HP/adenoma and control groups, P<0.05, and showed a further decrease with a higher degree of TNM staging. The tumor-free survival was shorter, and the relapse rate and mortality were higher in patients with positive methylation in the CRC group, P<0.05. Multivariate logistic regression analysis demonstrated that TNM staging and positive methylation were independent risk factors of mortality. In conclusion, higher methylation degree of CDX2 gene promoter resulted in decreased expression of CDX2 gene, and was closely associated with TNM staging and prognosis. TNM staging and positive methylation were independent risk factors of mortality for CRC patients.

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Nuclear transcription factor CDX2 inhibits gastric cancer-cell growth and reverses epithelial-to-mesenchymal transition in vitro and in vivo

Cited by 23 publications

References 38 publications

CDX2 and Reg IV Expression and Correlation in Gastric Cancer

CDX2 and Reg IV Expression and Correlation in Gastric Cancer

CDX2 and Reg IV expression and correlation in gastric cancer

Methylation of CDX2 gene promoter in the prediction of treatment efficacy in colorectal cancer

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