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COUP-TFII regulates metastasis of colorectal adenocarcinoma cells by modulating Snail1.

Bao Y, Gu D, Feng W, Sun X, Wang X, Zhang X, Shi Q, Cui G, Yu H, Tang C, Deng A - Br. J. Cancer (2014)

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: First Affiliated Hospital, Huzhou Teachers College, the First People's Hospital of Huzhou, Huzhou 313000, China.

ABSTRACT

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.

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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.
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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.


COUP-TFII regulates metastasis of colorectal adenocarcinoma cells by modulating Snail1.

Bao Y, Gu D, Feng W, Sun X, Wang X, Zhang X, Shi Q, Cui G, Yu H, Tang C, Deng A - Br. J. Cancer (2014)

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.
© Copyright Policy - open-access
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC4150277&req=5

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.

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: First Affiliated Hospital, Huzhou Teachers College, the First People's Hospital of Huzhou, Huzhou 313000, China.

ABSTRACT

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.

Show MeSH
Related in: MedlinePlus