Research Repository

See what's under the surface

FLYWCH1, a novel suppressor of nuclear β-catenin, regulates migration and morphology in colorectal cancer

Muhammad, Belal A.; Almozyan, Sheema; Babaei-Jadidi, Roya; Onyido, Emenike K.; Saadeddin, Anas; Hossein Kashfi, Seyed; Spencer-Dene, Bradley; Ilyas, Mohammad; Lourdusamy, Anbarasu; Behrens, Axel; Nateri, Abdolrahman S.

Authors

Belal A. Muhammad

Sheema Almozyan

Roya Babaei-Jadidi

Emenike K. Onyido

Anas Saadeddin

Seyed Hossein Kashfi

Bradley Spencer-Dene

Mohammad Ilyas

Anbarasu Lourdusamy

Axel Behrens

Abdolrahman S. Nateri

Abstract

Wnt/β-catenin signaling plays a critical role during development of both normal and malignant colorectal cancer tissues. Phosphorylation of β-catenin protein alters its trafficking and function. Such conventional allosteric regulation usually involves a highly specialized set of molecular interactions, which may specifically turn on a particular cell phenotype. This study identifies a novel transcription modulator with an FLYWCH/Zn-finger DNA-binding domain, called “FLYWCH1.” Using a modified yeast-2-hybrid based Ras-Recruitment system, it is demonstrated that FLYWCH1 directly binds to unphosphorylated (nuclear) β-catenin efficiently suppressing the transcriptional activity of Wnt/β-catenin signaling that cannot be rescued by TCF4. FLYWCH1 rearranges the transcriptional activity of β-catenin/TCF4 to selectively block the expression of specific downstream genes associated with colorectal cancer cell migration and morphology, including ZEB1, EPHA4, and E-cadherin. Accordingly, overexpression of FLYWCH1 reduces cell motility and increases cell attachment. The expression of FLYWCH1 negatively correlates with the expression level of ZEB1 and EPHA4 in normal versus primary and metastatic colorectal cancer tissues in patients. Thus, FLYWCH1 antagonizes β-catenin/TCF4 signaling during cell polarity/migration in colorectal cancer.

Journal Article Type Article
Publication Date Sep 6, 2018
Journal Molecular Cancer Research
Print ISSN 1541-7786
Electronic ISSN 1557-3125
Publisher American Association for Cancer Research
Peer Reviewed Peer Reviewed
DOI https://doi.org/10.1158/1541-7786.mcr-18-0262
Keywords Cancer research; Oncology; Molecular biology
Publisher URL http://mcr.aacrjournals.org/content/early/2018/09/06/1541-7786.MCR-18-0262.article-info

Files

This file is under embargo until Aug 10, 2019 due to copyright restrictions.



Downloadable Citations