COUP-TFII regulates metastasis of colorectal adenocarcinoma cells by modulating Snail1.
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Overexpression of COUP-TFII was required for cancer cells to metastasise in vivo.Chicken ovalbumin upstream promoter-transcription factor II regulated the transcription and expression of Snail1 by directly targeting the Snail1 promoter and regulated associated genes.Chicken ovalbumin upstream promoter-transcription factor II was found to be a biomarker associated with patient survival and colorectal cancer metastasis.
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PubMed Central - PubMed
Affiliation: First Affiliated Hospital, Huzhou Teachers College, the First People's Hospital of Huzhou, Huzhou 313000, China.
ABSTRACT
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Background: Chicken ovalbumin upstream promoter-transcription factor II (COUP-TFII, also known as NR2F2) promotes metastasis by functioning in the tumour microenvironment; however, the role of COUP-TFII in colorectal cancer remains unknown. Methods: Human colon adenocarcinoma tissues were collected to test COUP-TFII expression. Wound-healing and cell invasion assay were used to evaluate migration and invasion of cells. Chicken ovalbumin upstream promoter-transcription factor II and related protein expression was assessed by immunostaining, immunoblotting and real-time PCR assay. Tamoxifen-inducible COUP-TFII knockout mice were employed to test COUP-TFII functions on colon cancer metastasis in vivo. Results: Elevated expression of COUP-TFII in colorectal adenocarcinoma tissue correlated with overexpression of the Snail1 transcription factor. High COUP-TFII expression correlated with metastasis and shorter patient survival. Chicken ovalbumin upstream promoter-transcription factor II regulated the migration and invasion of cancer cells. With Snail1, COUP-TFII inhibited expression of adherence molecules such as ZO-1, E-cadherin and β-catenin in colorectal cancer cells. Overexpression of COUP-TFII was required for cancer cells to metastasise in vivo. Chicken ovalbumin upstream promoter-transcription factor II regulated the transcription and expression of Snail1 by directly targeting the Snail1 promoter and regulated associated genes. Conclusions: Chicken ovalbumin upstream promoter-transcription factor II was crucial for colorectal cancer metastasis and regulated cell migration and metastasis in conjunction with Snail1. Chicken ovalbumin upstream promoter-transcription factor II was found to be a biomarker associated with patient survival and colorectal cancer metastasis. Related in: MedlinePlus |
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fig3: Chicken ovalbumin upstream promoter-transcription factor II regulates metastasis of colon cancer in vivo in mice. Wild-type (WT) or COUP-TFII−/− mice were used to generate DMH/DSS-induced colon cancer models. (A) Typical appearance of metastatic foci on control livers (arrows). (B) Number of metastatic foci from A were calculated. *P<0.01 compared to WT. (C) Haematoxylin and eosin (H&E) staining for liver tissue. The arrow shows the tumour. Bar, 200 μm. (D) Immunohistochemistry was used to evaluate expression of E-cadherin and β-catenin from collected colon adenocarcinoma tissues. Bar, 50 μm. (E) Western blot showing expression of MMP2 and MMP9 in tumours from wild-type mice (WT) or COUP-TFII−/− mice (COUP-TFII−/−). (F) Control LOVO cells (CON) or COUP-TFII-depleted LOVO cells (COUP-TFII KD) were injected into spleens of nude mice. After 30 days, mice were killed and metastatic foci (arrows) on livers were examined. (G) Number of metastatic foci from F was calculated. *P<0.01 compared to CON. (H) H&E staining for liver tissue. Bar, 200 μm. Mentions: To study COUP-TFII function in vivo, we generated COUP-TFII knockout mice by using tamoxifen-inducible knockout system (Xie et al, 2011) and used them as DMH/DSS-induced mouse models of colonic carcinogenesis. Body weight was slightly decreased in DMH/DSS-treated mice compared to normal mice. The body weight of COUP-TFII−/− mice (n=10, 5 male and 5 female) was not different than COUP-TFII+/+ mice. There was no difference between male and female mice. In both control and COUP-TFII−/− mice, the incidence of tumours was 100% and the incidence of colorectal tumours was similar (Table 2). Metastatic tumours in the liver were observed in COUP-TFII+/+ mice treated with DMH/DSS after 40 weeks (Figure 3A). No metastatic tumours were found in the livers of COUP-TFII−/− mice treated with DMH/DSS, suggesting that COUP-TFII was crucial for colon cancer metastasis, not for the formation of tumours. |
View Article: PubMed Central - PubMed
Affiliation: First Affiliated Hospital, Huzhou Teachers College, the First People's Hospital of Huzhou, Huzhou 313000, China.
Background: Chicken ovalbumin upstream promoter-transcription factor II (COUP-TFII, also known as NR2F2) promotes metastasis by functioning in the tumour microenvironment; however, the role of COUP-TFII in colorectal cancer remains unknown.
Methods: Human colon adenocarcinoma tissues were collected to test COUP-TFII expression. Wound-healing and cell invasion assay were used to evaluate migration and invasion of cells. Chicken ovalbumin upstream promoter-transcription factor II and related protein expression was assessed by immunostaining, immunoblotting and real-time PCR assay. Tamoxifen-inducible COUP-TFII knockout mice were employed to test COUP-TFII functions on colon cancer metastasis in vivo.
Results: Elevated expression of COUP-TFII in colorectal adenocarcinoma tissue correlated with overexpression of the Snail1 transcription factor. High COUP-TFII expression correlated with metastasis and shorter patient survival. Chicken ovalbumin upstream promoter-transcription factor II regulated the migration and invasion of cancer cells. With Snail1, COUP-TFII inhibited expression of adherence molecules such as ZO-1, E-cadherin and β-catenin in colorectal cancer cells. Overexpression of COUP-TFII was required for cancer cells to metastasise in vivo. Chicken ovalbumin upstream promoter-transcription factor II regulated the transcription and expression of Snail1 by directly targeting the Snail1 promoter and regulated associated genes.
Conclusions: Chicken ovalbumin upstream promoter-transcription factor II was crucial for colorectal cancer metastasis and regulated cell migration and metastasis in conjunction with Snail1. Chicken ovalbumin upstream promoter-transcription factor II was found to be a biomarker associated with patient survival and colorectal cancer metastasis.