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

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


Belal A. Muhammad

Sheema Almozyan

Emenike K. Onyido

Anas Saadeddin

Seyed Hossein Kashfi

Bradley Spencer-Dene

Axel Behrens


© 2018 American Association for Cancer Research. Wnt/b-catenin signaling plays a critical role during development of both normal and malignant colorectal cancer tissues. Phosphorylation of b-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) b-catenin efficiently suppressing the transcriptional activity of Wnt/ b-catenin signaling that cannot be rescued by TCF4. FLYWCH1 rearranges the transcriptional activity of b-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 b-catenin/TCF4 signaling during cell polarity/migration in colorectal cancer. Implications: This study uncovers a new molecular mechanism by which FLYWCH1 with a possible tumor suppressive role represses b-catenin-induced ZEB1 and increases cadherin-mediated cell attachment preventing colorectal cancer metastasis.


Muhammad, B. A., Almozyan, S., Babaei-Jadidi, R., Onyido, E. K., Saadeddin, A., Kashfi, S. H., …Nateri, A. S. (2018). FLYWCH1, a novel suppressor of nuclear b-catenin, regulates migration and morphology in colorectal cancer. Molecular Cancer Research, 16(12), 1977-1990.

Journal Article Type Article
Acceptance Date Aug 1, 2018
Online Publication Date Aug 10, 2018
Publication Date Dec 1, 2018
Deposit Date Oct 29, 2018
Publicly Available Date Aug 11, 2019
Journal Molecular Cancer Research
Print ISSN 1541-7786
Electronic ISSN 1557-3125
Publisher American Association for Cancer Research
Peer Reviewed Peer Reviewed
Volume 16
Issue 12
Pages 1977-1990
Keywords Cancer research; Oncology; Molecular biology
Public URL
Publisher URL


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