A cascade-reaction enabled synergistic starvation/ROS-mediated/chemo-therapy was developed, and it exhibits a remarkable therapeutic efficacy without any external intervention.

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...

Aberrant changes in specific glycans have been shown to be associated with immunosurveillance, tumorigenesis, tumor progression and metastasis. In this study, the N-glycan profiling of membrane proteins from human breast cancer cell lines and tissues was detected using modified DNA sequencer-assisted fluorophore-assisted carbohydrate electrophoresis (DSA-FACE). The N-glycan profiles of membrane proteins were analyzed from 7 breast cancer cell lines and MCF 10A, as well as from 100 pairs of breast cancer and corresponding adjacent tissues. The results showed that, compared with the matched adjacent normal tissue samples, two biantennary N-glycans (NA2 and NA2FB) were significantly decreased (p <0.0001) in the breast cancer tissue samples, while the triantennary glycan (NA3FB) and a high-mannose glycan (M8) were dramatically increased (p = 0.001 and p <0.0001, respectively). Moreover, the alterations in these specific N-glycans occurred through the oncogenesis and progression of breast cancer. These results suggested that the modified method based on DSA-FACE is a high-throughput detection technology that is suited for analyzing cell surface N-glycans. These cell surface-specific N-glycans may be helpful in recognizing the mechanisms of tumor cell immunologic escape and could be potential targets for new breast cancer drugs.

High-throughput genomic technologies like lncRNA microarray and RNA-Seq often generate a set of lncRNAs of interest, yet little is known about the transcriptional regulation of the set of lncRNA genes. Here, based on ChIP-Seq peak lists of transcription factors (TFs) from ENCODE and annotated human lncRNAs from GENCODE, we developed a web-based interface titled “TF2lncRNA,” where TF peaks from each ChIP-Seq experiment are crossed with the genomic coordinates of a set of input lncRNAs, to identify which TFs present a statistically significant number of binding sites (peaks) within the regulatory region of the input lncRNA genes. The input can be a set of coexpressed lncRNA genes or any other cluster of lncRNA genes. Users can thus infer which TFs are likely to be common transcription regulators of the set of lncRNAs. In addition, users can retrieve all lncRNAs potentially regulated by a specific TF in a specific cell line of interest or retrieve all TFs that have one or more binding sites in the regulatory region of a given lncRNA in the specific cell line. TF2LncRNA is an efficient and easy-to-use web-based tool.