A Positive Feed-Forward Loop between LncRNA-CYTOR and Wnt/β-Catenin Signaling Promotes Metastasis of Colon Cancer

Researchers from Shanghai Jiao Tong University previously demonstrated that long non-coding RNA cytoskeleton regulator RNA (CYTOR), also known as Linc00152, was significantly overexpressed in colon cancer and conferred resistance to oxaliplatin-induced apoptosis. At the same time, elevated CYTOR expression was also reported in gastric cancer and exerted influences on epithelial-mesenchymal transition (EMT) markers. However, the precise mechanism by which CYTOR promotes the EMT phenotype and cancer metastasis remains poorly understood.

Here, the researchers showed that loss of epithelial characteristics and simultaneous gain of mesenchymal features correlated with CYTOR expression. Knockdown of CYTOR attenuated colon cancer cell migration and invasion. Conversely, ectopic expression of CYTOR induced an EMT program and enhanced metastatic properties of colon cancer cells. Mechanistically, the binding of CYTOR to cytoplasmic β-catenin impeded casein kinase 1 (CK1)-induced β-catenin phosphorylation that enabled it to accumulate and translocate to the nucleus. Reciprocally, β-catenin/TCF complex enhanced the transcription activity of CYTOR in nucleus, thus forming a positive feed-forward circuit. Moreover, elevated CYTOR, alone or combined with overexpression of nuclear β-catenin, was predictive of poor prognosis. These findings suggest that CYTOR promotes colon cancer EMT and metastasis by interacting with β-catenin, and the positive feed-forward circuit of CYTOR-β-catenin might be a useful therapeutic target in antimetastatic strategy.

lncrna

A Schematic Model of CYTOR-β-Catenin Signaling Circuit in Colon Cancer Cells

Yue B, Liu C, Sun H, Liu M, Song C, Cui R, Qiu S, Zhong M. (2018) A Positive Feed-Forward Loop between LncRNA-CYTOR and Wnt/β-Catenin Signaling Promotes Metastasis of Colon Cancer. Mol Ther [Epub ahead of print]. [abstract]

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