ERBB4 mutations in cancer and amyotrophic lateral sclerosis

摘要: ErbB receptor tyrosine kinases, epidermal growth factor (EGFR, also known as ErbB1), ErbB2 (HER2 or NEU), ErbB3 (HER3), and ErbB4 (HER4), transduce signals borne by extracellular ligands into central cellular responses such proliferation, survival, differentiation, apoptosis. Mutations in ERBB genes are frequently detected human malignant diseases of epithelial neural origin, making receptors important drug targets. Targeting EGFR has been successful eg. lung breast cancer, respectively, mutations these can be used to select patients that responsive the targeted treatment. Although somatic ERBB4 have found many high-incidence cancers melanoma, colorectal cancer germ-line linked neuronal disorders generally neglected a potential target. Thus, consequences on biology largely unknown. This thesis aimed elucidate functional assess clinical significance context amyotrophic lateral sclerosis. The results this study indicated cancer-associated promote aberrant function activating inducing qualitative changes signaling. increased survival decreased differentiation vitro, suggesting oncogenic. Importantly, potentially oncogenic were located various subdomains ErbB4, possibly providing explanation for characteristic scattered pattern ERBB4. demonstrated hereditary variation gene significant effect prognosis cancer. In addition, it was shown de novo predispose sclerosis inhibit activity. Together, suggest should considered novel target