Membrane-bound mucins belong to a heterogeneous family of large O-glycoproteins involved in numerous cancers and inflammatory diseases of the epithelium. Some of them are also involved in protein-protein interactions, with receptor tyrosine kinase ErbB2, and fundamental and clinical data showed that these complexes have a detrimental impact on cancer outcome, thus raising interest in therapeutic targeting. This paper aims to demonstrate that MUC3, MUC4, MUC12, MUC13, and MUC17 have a common evolutionary origin and share a common structural organization with EGF-like and SEA domains. Theoretical structure-function relationship analysis of the conserved domains indicated that the studied membrane-bound mucins share common biological properties along with potential specific functions. Finally, the potential druggability of these complexes is discussed, revealing ErbB2-related pathways of cell signaling to be targeted.

中文翻译：

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含有EGF的膜结合黏蛋白：一种隐藏的ErbB2靶向通路？

膜结合粘蛋白属于大的O-糖蛋白的异质家族，涉及多种上皮癌和炎性疾病。它们中的一些还与蛋白质与受体酪氨酸激酶ErbB2相互作用，基础和临床数据表明这些复合物对癌症的结果具有有害影响，因此引起了对治疗靶标的兴趣。本文旨在证明MUC3，MUC4，MUC12，MUC13和MUC17具有共同的进化起源，并具有类似EGF和SEA结构域的共同结构组织。保守结构域的理论结构-功能关系分析表明，所研究的膜结合粘蛋白具有共同的生物学特性以及潜在的特定功能。最后，