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Cell Signal. 2019 Sep;61:86-92. doi: 10.1016/j.cellsig.2019.05.009. Epub 2019 May 20.

Estrogen receptor alpha regulates the Wnt/β-catenin signaling pathway in colon cancer by targeting the NOD-like receptors.

Author information

1
MOE Joint International Research Laboratory of Animal Health and Food Safety, College of Veterinary Medicine, China Nanjing Agricultural University, Jiangsu Province, Nanjing 210095, China; Jiangsu Engineering Laboratory of Animal Immunology, Institute of Immunology, Nanjing Agricultural University, Jiangsu Province, Nanjing 210095, China.
2
MOE Joint International Research Laboratory of Animal Health and Food Safety, College of Veterinary Medicine, China Nanjing Agricultural University, Jiangsu Province, Nanjing 210095, China.
3
MOE Joint International Research Laboratory of Animal Health and Food Safety, College of Veterinary Medicine, China Nanjing Agricultural University, Jiangsu Province, Nanjing 210095, China. Electronic address: suquan.song@njau.edu.cn.

Abstract

It has been reported that estrogen receptors (ERs) participate in carcinogenesis by directly regulating NOD-like receptors (NLRs). However, the expression profiles of ERs and NLRs in tumor and the ER-NLR regulated signaling pathway are not clear. In this study, we summarized gene expression profiles of ERs and NLRs across normal and tumor tissue by comprehensive data mining. Then we explored the ER-NLR regulated signaling pathway by RNA sequencing (RNA-seq). The results showed that the NLRs and ERs were differentially expressed in different neoplasm tissues. Such expression discrepancies might influence inflammatory regulation and tumorigenesis. Importantly, we identified that ER-NLR regulate Wnt/β-catenin pathway in colon cancer. Taking colon adenocarcinoma (COAD) as example, we found that Wnt2b/LRP8/Dvl1/Axin2/GSK3a/APC/β-catenin genes were differentially expressed in ER-/- mouse colon tissue and colon cancer cells. The selective ERα antagonist could significantly decrease Wnt2b/LRP8/Dvl1 expression, increase destruction complex (Axin2/GSK3a/APC) expression, and promote degradation of β-catenin in colon carcinoma cell by inhibited NLRP3 expression. In short, the research demonstrates that NLRs are potential biomarkers for cancer, and ERs can regulate the Wnt/β-catenin signaling pathway in cancer by targeting the NLRs. Our results provide a possible signaling pathway in which ER-NLR is correlated with Wnt/β-catenin.

KEYWORDS:

Colon cancer; Estrogen receptors; NOD-like receptors; Wnt/β-catenin pathway

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