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

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.

• Authors: Y Bao, D Gu, W Feng, X Sun, X Wang, X Zhang, Q Shi, G Cui, H Yu, C Tang, A Deng
• Journal: British journal of cancer (Br J Cancer) Vol. 111 Issue 5 Pg. 933-43 (Aug 26 2014) ISSN: 1532-1827 [Electronic] England
• PMID: 25032732 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• COUP Transcription Factor II
• NR2F2 protein, human
• SNAI1 protein, human
• Snai1 protein, mouse
• Snail Family Transcription Factors
• Transcription Factors

Topics

• Adenocarcinoma (genetics, pathology)
• Animals
• COUP Transcription Factor II (genetics)
• Carcinogenesis (genetics, pathology)
• Cell Line, Tumor
• Cell Movement (genetics)
• Colorectal Neoplasms (genetics, pathology)
• Epithelial Cells (pathology)
• Female
• HT29 Cells
• Humans
• Mice
• Mice, Inbred C57BL
• Mice, Knockout
• Middle Aged
• Promoter Regions, Genetic (genetics)
• Snail Family Transcription Factors
• Transcription Factors (genetics)
• Transcription, Genetic (genetics)