Journal
ONCOTARGET
Volume 7, Issue 44, Pages 71136-71150Publisher
IMPACT JOURNALS LLC
DOI: 10.18632/oncotarget.12107
Keywords
colorectal cancer; cbl; Wnt
Categories
Funding
- NIH/NCI [RO1 CA175382]
- Sharon Anderson American Society of Nephrology
- Undergraduate Research Opportunities Program award (UROP) from Boston University
- [R21 CA191970]
- [R21 CA193958]
Ask authors/readers for more resources
Despite the loss of Adenomatous Polyposis Coli (APC) in a majority of colorectal cancers (CRC), not all CRCs bear hallmarks of Wnt activation, such as nuclear beta-catenin. This underscores the presence of other Wnt regulators that are important to define, given the pathogenic and prognostic roles of nuclear beta-catenin in human CRC. Herein, we investigated the effect of Casitas B-lineage lymphoma (c-Cbl) on nuclear beta-catenin, which is an oncoprotein upregulated in CRC due to loss-of-function APC or gain-of-function CTNNB1 mutations. Despite mechanistic rationale and recent discoveries of c-Cbl's mutations in solid tumors, little is known about its functional importance in CRC. Our study in a cohort of human CRC patients demonstrated an inverse correlation between nuclear beta-catenin and c-Cbl. Further investigation showed that the loss of c-Cbl activity significantly enhanced nuclear beta-catenin and CRC tumor growth in cell culture and a mouse xenograft model. c-Cbl interacted with and downregulated beta-catenin in a manner that was independent of CTNNB1 or APC mutation status. This study demonstrates a previously unrecognized function of c-Cbl as a negative regulator of CRC.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available