Carraway Kermit L, Funes Melanie, Workman Heather C, Sweeney Colleen
UC Davis Cancer Center, Sacramento, California 95817, USA.
Curr Top Dev Biol. 2007;78:1-22. doi: 10.1016/S0070-2153(06)78001-2.
Mucins are large, heavily O-glycosylated proteins expressed by epithelial tissues. The canonical function of membrane mucins is to provide protection to vulnerable epithelia by forming a steric barrier against assault, and by contributing to the formation of protective extracellular mucin gels. The aberrant overexpression of mucins is thought to contribute to tumor progression by allowing tumor cells to evade immune recognition, and by aiding in the breakdown of cell-cell and cell-matrix contacts to facilitate migration and metastasis. Recent evidence suggests that we should now modify our thinking about mucin function by considering their roles in signaling pathways leading to cellular growth control. Here we review the markedly divergent mechanisms by which membrane mucins, specifically MUC1 and MUC4, influence pathways contributing to cellular proliferation and survival. The cytoplasmic domain of MUC1 serves as a scaffold for the assembly of a variety of signaling proteins, while MUC4 influences the trafficking and localization of growth factor receptors, and hence their responses to external stimuli. We also discuss how tumor cells exploit these mechanisms to promote their own growth and metastasis.
黏蛋白是由上皮组织表达的大型、高度O-糖基化的蛋白质。膜结合黏蛋白的典型功能是通过形成空间屏障抵御攻击，并有助于形成保护性细胞外黏蛋白凝胶，从而为脆弱的上皮组织提供保护。黏蛋白的异常过表达被认为通过使肿瘤细胞逃避免疫识别，以及帮助破坏细胞间和细胞与基质的接触以促进迁移和转移，从而促进肿瘤进展。最近的证据表明，我们现在应该通过考虑它们在导致细胞生长控制的信号通路中的作用来修正我们对黏蛋白功能的认识。在这里，我们综述了膜结合黏蛋白，特别是MUC1和MUC4，影响细胞增殖和存活相关信号通路的显著不同机制。MUC1的细胞质结构域作为多种信号蛋白组装的支架，而MUC4影响生长因子受体的运输和定位，进而影响它们对外部刺激的反应。我们还讨论了肿瘤细胞如何利用这些机制来促进自身的生长和转移。
