The low-density lipoprotein receptor-related protein 1B (LRP1B) is known as a putative tumor suppressor. The decreased expression of LRP1B has been involved in multiple primary cancers in several studies. However, its expression and function in the carcinogenesis of renal cell cancer (RCC) remain unclear. In this study, we investigated the expression of LRP1B in RCC by in situ hybridization (ISH) and real-time polymerase chain reaction (qRT-PCR). Our results indicated that LRP1B was frequently downexpressed in human RCC tissue and cell lines, which involved both epigenetic events (DNA methylation and histone deacetylation) and N-terminal deletion of LRP1B. Moreover, we testified that knockdown of LRP1B by shRNA significantly promoted anchorage-independent growth, cell migration and invasion in HEK293 cells and renal cancer cells 127 in vitro. We further found that silencing of LRP1B altered the expression of focal adhesion complex-associated proteins, and Cdc42 ⁄ RhoA activities, which regulate the cytoskeleton dynamics. Taken together, these results strongly support that LRP1B may function as a tumor suppressor against renal cell cancer, and may regulate cell motility via RhoA ⁄ Cdc42 pathway and actin cytoskeleton reorganization in RCC. (Cancer Sci 2013; 104: 817-825) R enal cell carcinoma (RCC) is the most common kidney malignancy, and its incidence is increasing worldwide.(1)The early diagnosis and treatment of renal tumors have not reduced the mortality rate significantly, and in about 25-30% of cases, the localized tumors became spread around ultimately after surgical extirpation.(2-4) In addition, RCC is resistant to conventional therapies. Therefore, further elucidation of molecular mechanisms of RCC will be necessary for improving clinical diagnosis and effective therapeutic approaches.LRP1B, a member of the low-density lipoprotein (LDL) receptor family, was identified as a putative tumor suppressor. The down-expression of LRP1B was observed in multiple primary cancers. Liu et al.(5) first reported the homozygous deletions of the N terminal part and abnormal transcripts of LRP1B in non-small cell lung cancer. Subsequently, it was found that the homozygous loss and aberrant DNA methylation contributed to LRP1B silencing in esophageal squamous cell carcinoma, oral squamous cell carcinoma and gastric Cancer.(6-9) Yet, there is a lack of research on the expression and function of LRP1B in RCC.The LDL receptor family is a group of cell-surface transmembrane proteins.(10-12) LRP1B, along with LRP1 (LDL receptorrelated protein 1) and LRP2 (megalin) are the largest members of LDL receptor family with multiple ligand-binding sites. (11) LRP1B might participate in extracellular signal transduction via the different phosphorylation status of the cytoplasmic tail. (13) LRP1B shows 59% amino acid sequence identity with LRP1, and shares a nearly identical overall structure with LRP1, except for additional exon 68 and 90. Functionally, LRP1B was different with LRP1, as LRP1 showed increased expression in cancer ce...

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Endogenous or graft-derived oligodendrocytes promote myelination and aid in the recovery from central nervous system (CNS) injury. Regulatory mechanisms underlying neural myelination and remyelination in response to injury, including spinal cord injury (SCI), are unclear. In the present study, we demonstrated that TROY serves as an important negative regulator of oligodendrocyte development and that TROY inhibition augments the repair potential of oligodendrocyte precursor cell (OPC) graft for SCI. TROY expression was detected by reverse transcriptase-polymerase chain reaction in OPCs as well as in differentiated premature and mature oligodendrocytes of postnatal mice. Pharmacological inhibition or RNAi-induced knockdown of TROY promotes OPC differentiation, whereas overexpression of TROY dampens oligodendrocyte maturation. Further, treatment of cocultures of DRG neurons and OPCs with TROY inhibitors promotes myelination and myelinsheath-like structures. Mechanically, protein kinase C (PKC) signaling is involved in the regulation of the inhibitory effects of TROY. Moreover, in situ transplantation of OPCs with TROY knockdown leads to notable remyelination and neurological recovery in rats with SCI. Our results indicate that TROY negatively modulates remyelination in the CNS, and thus may be a suitable target for improving the therapeutic efficacy of cell transplantation for CNS injury.