The miR-1-NOTCH3-Asef pathway is important for colorectal tumor cell migration

The tumor suppressor adenomatous polyposis coli (APC) is mutated in sporadic and familial colorectal tumors. APC stimulates the activity of the Cdc42- and Rac1-specific guanine nucleotide exchange factor Asef and promotes the migration and invasion of colorectal tumor cells. Furthermore, Asef is ove...

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Bibliographic Details
Published in:PloS one 2013-11, Vol.8 (11), p.e80609-e80609
Main Authors: Furukawa, Shiori, Kawasaki, Yoshihiro, Miyamoto, Masaya, Hiyoshi, Masaya, Kitayama, Joji, Akiyama, Tetsu
Format: Article
Language:English
Subjects:
3' Untranslated regions
3' Untranslated Regions - genetics
Adenomatous polyposis coli
Caco-2 Cells
Cdc42 protein
Cell adhesion & migration
Cell Line
Cell migration
Cell Movement - genetics
Cell Movement - physiology
Cells (biology)
Chromatin Immunoprecipitation
Colorectal cancer
Colorectal Neoplasms - genetics
Colorectal Neoplasms - metabolism
Gastrointestinal diseases
Guanine
Guanine nucleotide exchange factor
Humans
Immunoglobulins
In Vitro Techniques
Intestine
Kinases
Laboratories
MicroRNA
MicroRNAs
MicroRNAs - genetics
MicroRNAs - metabolism
miRNA
Notch protein
Notch3 protein
Polyposis coli
Progenitor cells
Protein Binding
Proteins
Rac1 protein
Receptor, Notch3
Receptors, Notch - genetics
Receptors, Notch - metabolism
Ribonucleic acid
RNA
Signal Transduction - genetics
Signal Transduction - physiology
Signaling
Stem cells
Transcription factors
Tumor cells
Tumor suppressor genes
Tumorigenesis
Tumors
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Summary:The tumor suppressor adenomatous polyposis coli (APC) is mutated in sporadic and familial colorectal tumors. APC stimulates the activity of the Cdc42- and Rac1-specific guanine nucleotide exchange factor Asef and promotes the migration and invasion of colorectal tumor cells. Furthermore, Asef is overexpressed in colorectal tumors and is required for colorectal tumorigenesis. It is also known that NOTCH signaling plays critical roles in colorectal tumorigenesis and fate determination of intestinal progenitor cells. Here we show that NOTCH3 up-regulates Asef expression by activating the Asef promoter in colorectal tumor cells. Moreover, we demonstrate that microRNA-1 (miR-1) is down-regulated in colorectal tumors and that miR-1 has the potential to suppress NOTCH3 expression through direct binding to its 3'-UTR region. These results suggest that the miR-1-NOTCH3-Asef pathway is important for colorectal tumor cell migration and may be a promising molecular target for the treatment of colorectal tumors.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0080609