Multiple involvements of LRP-1 receptor in tumor progression

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 cons...

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Bibliographic Details
Published in:Pathologie biologie (Paris) 2009-11, Vol.57 (7-8), p.548-554
Main Authors: Langlois, B, Emonard, H, Martiny, L, Dedieu, S
Format: Article
Language:fre
Subjects:
Cell Division
Cell Survival
Cytoskeleton - pathology
Cytoskeleton - ultrastructure
Disease Progression
Endocytosis
Epithelial Cells - cytology
Humans
Low Density Lipoprotein Receptor-Related Protein-1 - drug effects
Low Density Lipoprotein Receptor-Related Protein-1 - physiology
Models, Biological
Neoplasm Metastasis - pathology
Neoplasm Metastasis - prevention & control
Neoplasms - pathology
Neoplasms - prevention & control
Tumor Suppressor Proteins - physiology
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Summary: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.
ISSN:1768-3114
DOI:10.1016/j.patbio.2008.07.015