Maintenance of Epithelial Stem Cells by Cbl Proteins
Abstract
The Cbl family E3 ubiquitin ligases are critical regulators of tyrosine kinase-mediated signal transduction, and we and others demonstrated that the Cbl family proteins were required to maintain the homeostasis of the hematopoietic stem cell compartment and disturbance of this critical regulatory pathway led to cancer in human and mice. However, their roles in the epithelial stem/progenitor cells has never been examined. Using the newly-established, in vitrodifferentiating hTERT-immortalized human mammary epithelial cell (hMEC) line, we demonstrated that loss of Cbl inhibited differentiation of epithelial cells. Our preliminary studies indicate that Cbl functions in multiple signaling pathways beyond the traditional EGFR-MEK-Erk pathway, which led to the complex phenotypes of Cbl deficiency in the epithelial compartment. Data from genetically-modified mouse models support that loss of Cbl and Cbl-b in the mammary epithelial compartment decreases the size of the stem/progenitor compartment and inhibits normal differentiation. Thus, unlike hematopoietic system, Cbl proteins are required for the survival and normal differentiation of mammary epithelial cells. These data highlight the tissue specificity of signal transduction pathways.
Document Details
- Document Type
- Technical Report
- Publication Date
- Sep 01, 2013
- Accession Number
- ADA598783
Entities
People
- Mayumi Naramura
Organizations
- University of Nebraska Medical Center