Langlois B, Emonard H, Martiny L, Dedieu S
Laboratoire Signalisation des récepteurs matriciels, CNRS UMR MEDyC 6237, université de Reims-Champagne-Ardenne, campus Moulin-de-la-Housse, BP 1039, 51687, Reims cedex 2, France.
Pathol Biol (Paris). 2009 Nov-Dec;57(7-8):548-54. doi: 10.1016/j.patbio.2008.07.015. Epub 2009 Feb 23.
Extensive proteolytic remodeling processes constitute a critical step during tumor progression. The endocytic receptor low-density lipoprotein receptor-related protein-1 (LRP-1), by its function in the clearance of multiple extracellular proteases involved in metastatic spreading, has long been considered as a putative tumor suppressor. Moreover, the receptor is likely to control the peritumoral microenvironment by internalization of growth factors and matricial proteins and could therefore participate to the control of signaling events involved in survival and proliferation of cancer cells. Nevertheless, recent data lead to reconsider the initially attributed antitumor properties of LRP-1. A more complex model seems to emerge in which LRP-1 could constitute a sensor of pericellular environment and regulate the membrane proteome dynamics. By its control of focal adhesions composition and turn-over, regulation of the cytoskeleton organization and integrin endocytic recycling, LRP-1 appears as a crucial actor of the epithelial-mesenchymal transition, thereby reinforcing the aggressive phenotype of malignant cells. LRP-1 partitioning into rafts and association with tissue-type and tumor grade specific intracellular scaffold proteins appear crucial to determine its function in tumor progression. Those emerging aspects present numerous promising perspectives in oncology and allow envisaging the development of innovative strategies of control of tumor progression through the targeting of LRP-1.
广泛的蛋白水解重塑过程是肿瘤进展过程中的关键步骤。内吞受体低密度脂蛋白受体相关蛋白1(LRP-1),因其在清除参与转移扩散的多种细胞外蛋白酶方面的功能,长期以来一直被视为一种假定的肿瘤抑制因子。此外,该受体可能通过内化生长因子和基质蛋白来控制肿瘤周围微环境,因此可能参与控制癌细胞存活和增殖所涉及的信号事件。然而,最近的数据导致人们重新审视LRP-1最初被赋予的抗肿瘤特性。一个更复杂的模型似乎正在出现,其中LRP-1可能构成细胞周围环境的传感器并调节膜蛋白质组动力学。通过控制粘着斑的组成和周转、调节细胞骨架组织和整合素内吞循环,LRP-1似乎是上皮-间质转化的关键参与者,从而强化了恶性细胞的侵袭性表型。LRP-1分配到脂筏中并与组织类型和肿瘤分级特异性细胞内支架蛋白结合,这对于确定其在肿瘤进展中的功能似乎至关重要。这些新出现的方面在肿瘤学中呈现出许多有前景的前景,并使得通过靶向LRP-1来设想控制肿瘤进展的创新策略的发展成为可能。