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Deleterious c-Cbl Exon Skipping Contributes to Human Glioma.


ABSTRACT: c-Cbl, a RING-type ubiquitin E3 ligase, downregulates various receptor tyrosine kinases (e.g., epidermal growth factor receptor (EGFR)), leading to inhibition of cell proliferation. Moreover, patients with myeloid neoplasm frequently harbor c-Cbl mutations, implicating the role of c-Cbl as a tumor suppressor. Recently, we have shown that c-Cbl downregulates αPix-mediated cell migration and invasion, and the lack of c-Cbl in the rat C6 and human A172 glioma cells is responsible for their malignant behavior. Here, we showed that c-Cbl exon skipping occurs in the glioma cells and the brain tissues from glioblastoma patients lacking c-Cbl. This exon skipping resulted in generation of two types of c-Cbl isoforms: type I lacking exon-9 and type II lacking exon-9 and exon-10. However, the c-Cbl i

SUBMITTER: Seong MW 

PROVIDER: S-EPMC4719003 | biostudies-literature | 2015 Jun

REPOSITORIES: biostudies-literature