Linking NRP2 With EMT and Chemoradioresistance in Bladder Cancer

Neuropilin-2 (NRP2) is a prognostic indicator for reduced survival in bladder cancer (BCa) patients. Together with its major ligand, vascular endothelial growth factor (VEGF)-C, NRP2 expression is a predictive factor for treatment outcome in response to radiochemotherapy in BCa patients who underwent transurethral resection. Therefore, we investigated the benefit of combining cisplatin-based chemotherapy with irradiation treatment in the BCa cell line RT112 exhibiting or lacking endogenous NRP2 expression in order to evaluate NRP2 as potential therapeutic target. We have identified a high correlation of NRP2 and the glioma-associated oncogene family zinc finger 2 (GLI2) transcripts in the cancer genome atlas (TCGA) cohort of BCa patients and a panel of 15 human BCa cell lines. Furthermore, we used in vitro BCa models to show the transforming growth factor-beta 1 (TGFβ1)-dependent regulation of NRP2 and GLI2 expression levels. Since NRP2 was shown to bind TGFβ1, associate with TGFβ receptors, and enhance TGFβ1 signaling, we evaluated downstream signaling pathways using an epithelial-to-mesenchymal transition (EMT)-assay in combination with a PCR profiling array containing 84 genes related to EMT. Subsequent target validation in NRP2 knockout and knockdown models revealed secreted phosphoprotein 1 (SPP1/OPN/Osteopontin) as a downstream target positively regulated by NRP2.
Source: Frontiers in Oncology - Category: Cancer & Oncology Source Type: research

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In this study, we found that Lnc-OC1 was significantly higher in PCOS granulosa cells (GCs) compared to non-PCOS GCs. Lnc-OC1 knockdown inhibited cell viability and promoted cell apoptosis, expression of aromatase mRNA and production of estradiol in KGN cells. In PCOS mice, Lnc-OC1 promoted the serum insulin release, production of angiogenesis-related factors and IκBα phosphorylation, which could be partially restored by Lnc-OC1 shRNA. These results suggest that Lnc-OC1 plays an important part in the pathogenesis of PCOS.
Source: Molecular and Cellular Endocrinology - Category: Endocrinology Source Type: research
Publication date: Available online 15 February 2020Source: Pharmacological ResearchAuthor(s): Yuanlin Wu, Jing Li, Parham Jabbarzadeh Kaboli, Jing Shen, Xu Wu, Yueshui Zhao, Huijiao Ji, Fukuan Du, Yejiang Zhou, Yongzhou Wang, Hanyu Zhang, Jianhua Yin, Qinglian Wen, Chi Hin Cho, Mingxing Li, Zhangang XiaoAbstractNatural killer (NK) cells are immune cells which are able to kill tumor and virus-infected cells and play an important role in both innate immunity and acquired immunity. Tumor immunotherapy is an emerging model of tumor treatment in the clinic. It is a re-emerging type of anticancer immunotherapy with the purpose o...
Source: Pharmacological Research - Category: Drugs & Pharmacology Source Type: research
Al-Dayel F, Al-Kuraya KS Abstract Sanger Sequencing and immunohistochemistry was employed to investigate the TERT promoter mutations and TERT protein expression with their association to clinicopathological characteristics in over 2200 samples of Middle Eastern origin from 13 different types of cancers. The TERT promoter mutations were most frequently present in bladder cancer (68.6%), followed by central nervous system tumors (28.7%), thyroid cancer (15.4%), prostate cancer (9.3%), endometrial carcinoma (3.7%), rhabdomyosarcoma (1.4%), colorectal cancer (1%), epithelial ovarian carcinoma (0.7%) and breast cancer ...
Source: Genomics - Category: Genetics & Stem Cells Authors: Tags: Genomics Source Type: research
In conclusion, BLACAT1 may serve as an oncogenic lncRNA in glioma progression via activation of the Wnt/β-catenin signaling pathway. Therefore, BLACAT1 may be a novel therapeutic target for glioma treatment. PMID: 31086604 [PubMed]
Source: Experimental and Therapeutic Medicine - Category: General Medicine Tags: Exp Ther Med Source Type: research
Michal Yalon1†, Amos Toren1,2†, Dina Jabarin2, Edna Fadida3, Shlomi Constantini3 and Ruty Mehrian-Shai1* 1Pediatric Hemato-Oncology, Edmond and Lilly Safra Children's Hospital and Cancer Research Center, Sheba Medical Center, Ramat Gan, Israel 2The Sackler School of Medicine, Tel-Aviv University, Tel Aviv, Israel 3Department of Pediatric Neurosurgery, Dana Children's Hospital, Tel-Aviv-Sourasky Medical Center, Tel Aviv, Israel Pediatric brain tumors are the most common solid tumor type and the leading cause of cancer-related death in children. The immune system plays an important r...
Source: Frontiers in Oncology - Category: Cancer & Oncology Source Type: research
Conclusions Several model systems are now available to characterize the MSC-tumour interplay in the TME. These offer early promise in establishing robust preclinical platforms for the identification of crucial molecular pathways and for the assessment of clinical efficacy of novel drugs to inhibit cancer development and progression. However, selection of the right model for a given study should be shaped on the purpose, and should also consider fixed biological, biochemical, and biophysical parameters according to the specific tumour type. Finally, in order to get reliable and useful results to be translated to the clinic...
Source: Frontiers in Oncology - Category: Cancer & Oncology Source Type: research
Xiaohui Xu, Congmin Ma, Zhihui Duan, Yanjiao Du and Chao Liu* Department of Neurology, Luoyang Central Hospital Affiliated to Zhengzhou University, Luoyang, China Oxidized-low density lipoprotein (ox-LDL) can induce injury of endothelial cells, causing atherosclerosis, which is an important initial event in several cardiovascular diseases. Long non-coding RNAs (lncRNAs) have emerged as regulators of diverse biological processes, but their specific biological functions and biochemical mechanisms in ox-LDL-induced endothelial cell injury have not been well investigated. Here, we describe the initial functional an...
Source: Frontiers in Pharmacology - Category: Drugs & Pharmacology Source Type: research
In conclusion, osmotic burst of inflated complement-damaged cells may occur, but these bursts are most likely a consequence of metabolic collapse of the cell rather than the cause of cell death. The Complement Cell Death Mediator: A Concerted Action of Toxic Moieties Membrane pores caused by complement were first visualized by electron microscopy on red blood cell membranes as large ring structures (22). Similar lesions were viewed on E. coli cell walls (23). Over the years, ample information on the fine ultrastructure of the MAC that can activate cell death has been gathered (24) and has been recently further examined (...
Source: Frontiers in Immunology - Category: Allergy & Immunology Source Type: research
MAPK4 is an atypical MAPK. Currently, little is known about its physiological function and involvement in diseases, including cancer. A comprehensive analysis of 8887 gene expression profiles in The Cancer Genome Atlas (TCGA) revealed that MAPK4 overexpression correlates with decreased overall survival, with particularly marked survival effects in patients with lung adenocarcinoma, bladder cancer, low-grade glioma, and thyroid carcinoma. Interestingly, human tumor MAPK4 overexpression also correlated with phosphorylation of AKT, 4E-BP1, and p70S6K, independent of the loss of PTEN or mutation of PIK3CA. This led us to exami...
Source: Journal of Clinical Investigation - Category: Biomedical Science Authors: Source Type: research
In conclusion, the application prospect of FOXQ1 in tumors is hopeful. PMID: 27176124 [PubMed - as supplied by publisher]
Source: International Journal of Oncology - Category: Cancer & Oncology Authors: Tags: Int J Oncol Source Type: research
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