Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts 02115, USA.
Nat Rev Cancer. 2009 Dec;9(12):874-85. doi: 10.1038/nrc2761.
Epithelia are protected from adverse conditions by a mucous barrier. The secreted and transmembrane mucins that constitute the mucous barrier are largely unrecognized as effectors of carcinogenesis. However, both types of mucins are intimately involved in inflammation and cancer. Moreover, diverse human malignancies overexpress transmembrane mucins to exploit their role in signalling cell growth and survival. Mucins have thus been identified as markers of adverse prognosis and as attractive therapeutic targets. Notably, the findings that certain transmembrane mucins induce transformation and promote tumour progression have provided the experimental basis for demonstrating that inhibitors of their function are effective as anti-tumour agents in preclinical models.
上皮细胞受到粘液屏障的保护,免受不利条件的影响。构成粘液屏障的分泌型和跨膜粘蛋白在很大程度上未被认为是致癌作用的效应物。然而,这两种类型的粘蛋白都与炎症和癌症密切相关。此外,多种人类恶性肿瘤过度表达跨膜粘蛋白,以利用其在信号转导细胞生长和存活中的作用。因此,粘蛋白被确定为不良预后的标志物,并成为有吸引力的治疗靶点。值得注意的是,某些跨膜粘蛋白诱导转化并促进肿瘤进展的发现为证明其功能抑制剂在临床前模型中作为抗肿瘤药物是有效的提供了实验基础。