Fig. 2

Low-density LRP1-mediated cell signaling pathways. LRP1 regulates several signaling pathways in a phosphorylation-dependent manner. These pathways are involved in several processes of tumorigenesis and progression. Binding of LRP1 to platelet-derived growth factor (PDGF) receptor activates the mitogen-activated protein kinase (MAPK) signaling pathway, which subsequently activates the extracellular signal-regulated kinase (ERK) pathway and inhibits c-jun N-terminal kinase (JNK), resulting in cancer cell invasion and proliferation. In addition, ERK increases the transcriptional levels of matrix metalloproteinase (MMP)-2 and MMP-9, which drive cancer cell invasion. LRP1 activates the serine/threonine protein kinase (AKT) signaling pathway and insulin receptor (IR), which inhibits cancer cell apoptosis. LRP1 binds to the novel extracellular heat shock protein 90 (eHsp90) and forms an eHsp90-LRP1 signaling complex, which stimulates glioblastoma multiforme cell motility and invasion via AKT-dependent phosphorylation at S897 (p-EphA2S897). The eHsp90 signaling regulates AKT activation and facilitates recruitment of LRP1 to the receptor tyrosine kinase EphA2