Khademi Rahele, Malekzadeh Hossein, Bahrami Sara, Saki Najmaldin, Khademi Reyhane, Villa-Diaz Luis G
Systematic Review and Meta-Analysis Expert Group (SRMEG), Universal Scientific Education and Research Network (USERN), Tehran 1419733151, Iran.
Immunology Board for Transplantation and Cell-Based Therapeutics (Immuno_TACT), Universal Scientific Education and Research Network (USERN), Tehran 1419733151, Iran.
Cancers (Basel). 2023 Jul 2;15(13):3466. doi: 10.3390/cancers15133466.
Over the past decades, our knowledge of integrins has evolved from being understood as simple cell surface adhesion molecules to receptors that have a complex range of intracellular and extracellular functions, such as delivering chemical and mechanical signals to cells. Consequently, they actively control cellular proliferation, differentiation, and apoptosis. Dysregulation of integrin signaling is a major factor in the development and progression of many tumors. Many reviews have covered the broader integrin family in molecular and cellular studies and its roles in diseases. Nevertheless, further understanding of the mechanisms specific to an individual subunit of different heterodimers is more useful. Thus, we describe the current understanding of and exploratory investigations on the α6-integrin subunit (CD49f, VLA6; encoded by the gene ) in normal and cancer cells. The roles of ITGA6 in cell adhesion, stemness, metastasis, angiogenesis, and drug resistance, and as a diagnosis biomarker, are discussed. The role of ITGA6 differs based on several features, such as cell background, cancer type, and post-transcriptional alterations. In addition, exosomal ITGA6 also implies metastatic organotropism. The importance of ITGA6 in the progression of a number of cancers, including hematological malignancies, suggests its potential usage as a novel prognostic or diagnostic marker and useful therapeutic target for better clinical outcomes.
在过去几十年里，我们对整合素的认识已从单纯的细胞表面黏附分子演变为具有一系列复杂细胞内和细胞外功能的受体，比如向细胞传递化学和机械信号。因此，它们积极调控细胞增殖、分化和凋亡。整合素信号失调是许多肿瘤发生和发展的主要因素。许多综述已涵盖整合素家族在分子和细胞研究方面的更广泛内容及其在疾病中的作用。然而，进一步了解不同异二聚体单个亚基的特定机制更具价值。因此，我们描述了目前对α6整合素亚基（CD49f，VLA6；由该基因编码）在正常细胞和癌细胞中的认识及探索性研究。讨论了ITGA6在细胞黏附、干性、转移、血管生成和耐药性方面的作用，以及作为诊断生物标志物的作用。ITGA6的作用因细胞背景、癌症类型和转录后改变等多种特征而异。此外，外泌体ITGA6也意味着转移的器官嗜性。ITGA6在包括血液系统恶性肿瘤在内的多种癌症进展中的重要性表明，它有潜力作为一种新型的预后或诊断标志物，以及作为改善临床结果的有用治疗靶点。
