Multiple involvements of LRP-1 receptor in tumor progression
Multiple involvements of LRP-1 receptor in tumor progression
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DOI：
10.1016/j.patbio.2008.07.015
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发表时间：
2009-11-01
影响因子：
--
通讯作者：
Dedieu, S.
中科院分区：
文献类型：
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作者：
Langlois, B.;Emonard, H.;Dedieu, S.
广泛的蛋白水解重塑过程构成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）通过其清除参与转移扩散的多种细胞外蛋白酶的功能，长期以来被认为是公认的肿瘤抑制因子。此外，该受体可能通过生长因子和基质蛋白的内化来控制肿瘤周围的微环境，因此可能参与控制涉及癌细胞存活和增殖的信号传导事件。然而，最近的数据导致重新考虑LRP-1最初归因的抗肿瘤特性。一个更复杂的模型似乎出现了，其中LRP-1可以构成细胞周围环境的传感器和调节膜蛋白质组动力学。通过其对粘着斑组成和翻转的控制、对细胞骨架组织和整联蛋白内吞再循环的调节，LRP-1似乎是上皮-间质转化的关键作用者，从而增强恶性细胞的侵袭性表型。LRP-1分配到筏和与组织类型和肿瘤等级特异性细胞内支架蛋白的关联似乎对确定其在肿瘤进展中的功能至关重要。这些新出现的方面在肿瘤学中呈现出许多有希望的前景，并允许设想通过靶向LRP-1来控制肿瘤进展的创新策略的发展。(C)2008年，Elsevier Masson SAS。图斯所有权保留。
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. (C) 2008 Elsevier Masson SAS. Tous droits reserves.