Additionally, loss-of-function mutations in the CBL gene are associated with the development of cancers since CBL has tumor suppressor functions through both ubiquitylation and degradation of RTKs and inhibition of the PI3K signaling pathway (37), indicating that CBL or CBL-B mutations might be involved in the pathogenesis of autoreactive inflammatory disorders and cancers in humans (Figure 2). This evidence concerns the gene CBLB and cancer.