c-Cbl: An Important Regulator and a Target in Angiogenesis and Tumorigenesis

Abstract

Casitas B lineage lymphoma (c-Cbl) is a multifunctional protein with a ubiquitin E3 ligase activity capable of degrading diverse sets of proteins. Although previous work had focused mainly on c-Cbl mutations in humans with hematological malignancies, recent emerging evidence suggests a critical role of c-Cbl in angiogenesis and human solid organ tumors. The combination of its unique structure, modular function, and ability to channelize cues from a rich network of signaling cascades, empowers c-Cbl to assume a central role in these disease models. This review consolidates the structural and functional insights based on recent studies that highlight c-Cbl as a target with tantalizing therapeutic potential in various models of angiogenesis and tumorigenesis.

Keywords

• angiogenesis
• tumors
• ubiquitination
• proteasomal degradation
• c-Cbl
• RTK
• non-RTK
• VEGFR
• FGFR
• PDGFR
• EGFR
• c-Met
• Wnt signaling
• β–catenin
• PLCγ1