Prieto-Fernández Llara, Menéndez Sofía T, Otero-Rosales María, Montoro-Jiménez Irene, Hermida-Prado Francisco, García-Pedrero Juana M, Álvarez-Teijeiro Saúl
Department of Otolaryngology, Hospital Universitario Central de Asturias and Instituto de Investigación Sanitaria Del Principado de Asturias (ISPA), Instituto Universitario de Oncología Del Principado de Asturias (IUOPA), University of Oviedo, Oviedo, Spain.
CIBERONC, Instituto de Salud Carlos III, Madrid, Spain.
Front Cell Dev Biol. 2022 Sep 28;10:1009908. doi: 10.3389/fcell.2022.1009908. eCollection 2022.
Annexins are an extensive superfamily of structurally related calcium- and phospholipid-binding proteins, largely conserved and widely distributed among species. Twelve human annexins have been identified, referred to as Annexin A1-13 (A12 remains as of yet unassigned), whose genes are spread throughout the genome on eight different chromosomes. According to their distinct tissue distribution and subcellular localization, annexins have been functionally implicated in a variety of biological processes relevant to both physiological and pathological conditions. Dysregulation of annexin expression patterns and functions has been revealed as a common feature in multiple cancers, thereby emerging as potential biomarkers and molecular targets for clinical application. Nevertheless, translation of this knowledge to the clinic requires in-depth functional and mechanistic characterization of dysregulated annexins for each individual cancer type, since each protein exhibits varying expression levels and phenotypic specificity depending on the tumor types. This review specifically and thoroughly examines the current knowledge on annexin dysfunctions in carcinogenesis. Hence, available data on expression levels, mechanism of action and pathophysiological effects of Annexin A1-13 among different cancers will be dissected, also further discussing future perspectives for potential applications as biomarkers for early diagnosis, prognosis and molecular-targeted therapies. Special attention is devoted to head and neck cancers (HNC), a complex and heterogeneous group of aggressive malignancies, often lately diagnosed, with high mortality, and scarce therapeutic options.
膜联蛋白是一个结构相关的钙结合和磷脂结合蛋白的广泛超家族，在物种间高度保守且分布广泛。已鉴定出12种人类膜联蛋白，称为膜联蛋白A1 - 13（A12尚未被指定），其基因分布在8条不同染色体的整个基因组中。根据其独特的组织分布和亚细胞定位，膜联蛋白在与生理和病理状况相关的多种生物学过程中发挥功能作用。膜联蛋白表达模式和功能的失调已被揭示为多种癌症的共同特征，从而成为临床应用的潜在生物标志物和分子靶点。然而，将这些知识转化为临床应用需要针对每种癌症类型对失调的膜联蛋白进行深入的功能和机制表征，因为每种蛋白根据肿瘤类型表现出不同的表达水平和表型特异性。本综述特别全面地审视了关于膜联蛋白在致癌作用中功能失调的现有知识。因此，将剖析不同癌症中膜联蛋白A1 - 13的表达水平、作用机制和病理生理效应的现有数据，还将进一步讨论其作为早期诊断、预后和分子靶向治疗生物标志物的潜在应用的未来前景。特别关注头颈癌（HNC），这是一组复杂且异质性的侵袭性恶性肿瘤，通常诊断较晚，死亡率高，治疗选择有限。
