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Title: Prosaposin is a biomarker of mesenchymal glioblastoma and regulates mesenchymal transition through the TGF‐β1/Smad signaling pathway

Journal Article · · Journal of Pathology
DOI: https://doi.org/10.1002/path.5278 · OSTI ID:1514753
 [1];  [2];  [3];  [2];  [4];  [5];  [6];  [2];  [7];  [8];  [7]; ORCiD logo [2]
  1. Department of Neurosurgery The First Hospital of China Medical University Shenyang City PR China, Department of Neurosurgery Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine Shanghai PR China
  2. Department of Neurosurgery The First Hospital of China Medical University Shenyang City PR China
  3. Department of Neurosurgery Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine Shanghai PR China
  4. College of Life and Health Sciences, Northeastern University Shenyang PR China
  5. Department of Medical Oncology Cancer Hospital of China Medical University Shenyang PR China
  6. Department of Neurosurgery/Neuro‐oncology SunYat‐sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine Guangzhou PR China
  7. The First laboratory of cancer institute, the First Hospital of China Medical University Shenyang City PR China
  8. International Education College, Liaoning University of Traditional Chinese Medicine Shenyang City PR China

Abstract Mesenchymal glioblastoma (GBM) is the most aggressive subtype of GBM. Our previous study found that neurotrophic factor prosaposin (PSAP) is highly expressed and secreted in glioma and can promote the growth of glioma. The role of PSAP in mesenchymal GBM is still unclear. In this study, bioinformatic analysis, western blotting and RT‐qPCR were used to detect the expression of PSAP in different GBM subtypes. Human glioma cell lines and patient‐derived glioma stem cells were studied in vitro and in vivo , revealing that mesenchymal GBM expressed and secreted the highest level of PSAP among four subtypes of GBM, and PSAP could promote GBM invasion and epithelial–mesenchymal transition (EMT)‐like processes in vivo and in vitro . Bioinformatic analysis and western blotting showed that PSAP mainly played a regulatory role in GBM invasion and EMT‐like processes via the TGF‐β1/Smad signaling pathway. In conclusion, the overexpression and secretion of PSAP may be an important factor causing the high invasiveness of mesenchymal GBM. PSAP is therefore a potential target for the treatment of mesenchymal GBM. © 2019 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd

Sponsoring Organization:
USDOE
OSTI ID:
1514753
Journal Information:
Journal of Pathology, Journal Name: Journal of Pathology Journal Issue: 1 Vol. 249; ISSN 0022-3417
Publisher:
Wiley Blackwell (John Wiley & Sons)Copyright Statement
Country of Publication:
United Kingdom
Language:
English

References (53)

Amplification and overexpression of prosaposin in prostate cancer journal January 2005
FAT1 modulates EMT and stemness genes expression in hypoxic glioblastoma: FAT1 as a novel regulator of stemness and EMT in glioblastoma journal October 2017
Prosaposin is a novel androgen-regulated gene in prostate cancer cell line LNCaP journal January 2007
Prosaposin is an AR-target gene and its neurotrophic domain upregulates AR expression and activity in prostate stromal cells journal May 2008
Protein precipitation of diluted samples in SDS-containing buffer with acetone leads to higher protein recovery and reproducibility in comparison with TCA/acetone approach journal May 2016
Serum prosaposin levels are increased in patients with advanced prostate cancer journal May 2011
TSC22D1 and PSAP predict clinical outcome of tamoxifen treatment in patients with recurrent breast cancer journal February 2008
Temozolomide sensitizes stem-like cells of glioma spheres to TRAIL-induced apoptosis via upregulation of casitas B-lineage lymphoma (c-Cbl) protein journal July 2015
Saposins: structure, function, distribution, and molecular genetics. journal September 1992
MiR-181b suppresses proliferation of and reduces chemoresistance to temozolomide in U87 glioma stem cells journal November 2010
TGF-β promotes glioma cell growth via activating Nodal expression through Smad and ERK1/2 pathways journal January 2014
Identification of prosaposin and transgelin as potential biomarkers for gallbladder cancer using quantitative proteomics journal April 2014
TGF-β-mediated repression of MST1 by DNMT1 promotes glioma malignancy journal October 2017
The protective role of prosaposin and its receptors in the nervous system journal October 2014
Molecular subclasses of high-grade glioma predict prognosis, delineate a pattern of disease progression, and resemble stages in neurogenesis journal March 2006
Hypoxia-Inducible Factors Regulate Tumorigenic Capacity of Glioma Stem Cells journal June 2009
Integrated Genomic Analysis Identifies Clinically Relevant Subtypes of Glioblastoma Characterized by Abnormalities in PDGFRA, IDH1, EGFR, and NF1 journal January 2010
Mesenchymal Differentiation Mediated by NF-κB Promotes Radiation Resistance in Glioblastoma journal September 2013
GPR56/ADGRG1 Inhibits Mesenchymal Differentiation and Radioresistance in Glioblastoma journal November 2017
Prosaposin promotes the proliferation and tumorigenesis of glioma through toll-like receptor 4 (TLR4)-mediated NF-κB signaling pathway journal November 2018
Autophagy induction impairs migration and invasion by reversing EMT in glioblastoma cells journal May 2015
Tumour-infiltrating CD4+ and CD8+ lymphocytes as predictors of clinical outcome in glioma journal April 2014
Targeting glioma stem cells through combined BMI1 and EZH2 inhibition journal October 2017
A novel interaction of PAK4 with PPARγ to regulate Nox1 and radiation-induced epithelial-to-mesenchymal transition in glioma journal May 2017
Stevioside attenuates isoproterenol-induced mouse myocardial fibrosis through inhibition of the myocardial NF-κB/TGF-β1/Smad signaling pathway journal January 2019
Prosaposin Facilitates Sciatic Nerve Regeneration In Vivo journal May 1996
The MicroRNA-23b/27b/24 Cluster Promotes Breast Cancer Lung Metastasis by Targeting Metastasis-suppressive Gene Prosaposin journal June 2014
Prosaposin facilitates sortilin-independent lysosomal trafficking of progranulin journal September 2015
Sphingolipid activator proteins: proteins with complex functions in lipid degradation and skin biogenesis journal June 2001
A multigene predictor of outcome in glioblastoma journal October 2009
TGF-β Family Signaling in Tumor Suppression and Cancer Progression journal February 2017
Cancer stem cells in glioblastoma journal June 2015
Prosaposin, a regulator of estrogen receptor alpha, promotes breast cancer growth journal August 2012
Development of a prosaposin-derived therapeutic cyclic peptide that targets ovarian cancer via the tumor microenvironment journal March 2016
Wnt5a Drives an Invasive Phenotype in Human Glioblastoma Stem-like Cells journal December 2016
Krüppel-like Transcription Factor KLF10 Suppresses TGFβ-Induced Epithelial-to-Mesenchymal Transition via a Negative Feedback Mechanism journal March 2017
Mechano-Signal Transduction in Mesenchymal Stem Cells Induces Prosaposin Secretion to Drive the Proliferation of Breast Cancer Cells journal September 2017
S100A4 Is a Biomarker and Regulator of Glioma Stem Cells That Is Critical for Mesenchymal Transition in Glioblastoma journal August 2017
Bivalent Chromatin Domains in Glioblastoma Reveal a Subtype-Specific Signature of Glioma Stem Cells journal March 2018
Bone Marrow–Derived Gr1 + Cells Can Generate a Metastasis-Resistant Microenvironment Via Induced Secretion of Thrombospondin-1 journal April 2013
TGF-β1 Induces EMT in Bovine Mammary Epithelial Cells Through the TGFβ1/Smad Signaling Pathway journal January 2017
Prosaposin down-modulation decreases metastatic prostate cancer cell adhesion, migration, and invasion journal January 2010
ARL2 overexpression inhibits glioma proliferation and tumorigenicity via down-regulating AXL journal May 2018
NFAT1-regulated IL6 signalling contributes to aggressive phenotypes of glioma journal December 2017
TGF-β2 initiates autophagy via Smad and non-Smad pathway to promote glioma cells’ invasion journal November 2017
Prosaposin activates the androgen receptor and potentiates resistance to endocrine treatment in breast cancer journal September 2015
Mesenchymal stem cells in breast cancer: response to chemical and mechanical stimuli journal November 2017
Glioblastoma: new therapeutic strategies to address cellular and genomic complexity journal December 2017
Prosaposin-derived peptide alleviates ischaemia-induced hearing loss journal December 2012
Astilbin Inhibits High Glucose-Induced Inflammation and Extracellular Matrix Accumulation by Suppressing the TLR4/MyD88/NF-κB Pathway in Rat Glomerular Mesangial Cells journal October 2018
HMGB1 induces lung fibroblast to myofibroblast differentiation through NF-κB-mediated TGF-β1 release journal March 2017
TGFβ1 Promotes Gemcitabine Resistance through Regulating the LncRNA-LET/NF90/miR-145 Signaling Axis in Bladder Cancer journal January 2017
Mesenchymal glioblastoma constitutes a major ceRNA signature in the TGF-β pathway journal January 2018