scholarly journals Plasma Membrane Ca2+ ATPase Isoform 4 (PMCA4) Has an Important Role in Numerous Hallmarks of Pancreatic Cancer

Cancers ◽  
2020 ◽  
Vol 12 (1) ◽  
pp. 218 ◽  
Author(s):  
Pishyaporn Sritangos ◽  
Eduardo Pena Alarcon ◽  
Andrew D. James ◽  
Ahlam Sultan ◽  
Daniel A. Richardson ◽  
...  
Keyword(s):  
Plasma Membrane ◽  
Cell Migration ◽  
Pancreatic Ductal Adenocarcinoma ◽  
Patient Survival ◽  
Ductal Adenocarcinoma ◽  
Plasma Membrane Calcium Atpase ◽  
Cancer Hallmarks ◽  
Poor Patient ◽  
Resistance Data ◽  
Poor Patient Survival

Pancreatic ductal adenocarcinoma (PDAC) is largely resistant to standard treatments leading to poor patient survival. The expression of plasma membrane calcium ATPase-4 (PMCA4) is reported to modulate key cancer hallmarks including cell migration, growth, and apoptotic resistance. Data-mining revealed that PMCA4 was over-expressed in pancreatic ductal adenocarcinoma (PDAC) tumors which correlated with poor patient survival. Western blot and RT-qPCR revealed that MIA PaCa-2 cells almost exclusively express PMCA4 making these a suitable cellular model of PDAC with poor patient survival. Knockdown of PMCA4 in MIA PaCa-2 cells (using siRNA) reduced cytosolic Ca2+ ([Ca2+]i) clearance, cell migration, and sensitized cells to apoptosis, without affecting cell growth. Knocking down PMCA4 had minimal effects on numerous metabolic parameters (as assessed using the Seahorse XF analyzer). In summary, this study provides the first evidence that PMCA4 is over-expressed in PDAC and plays a role in cell migration and apoptotic resistance in MIA PaCa-2 cells. This suggests that PMCA4 may offer an attractive novel therapeutic target in PDAC.

scholarly journals Proteomic analyses of ECM during pancreatic ductal adenocarcinoma progression reveal different contributions by tumor and stromal cells

2019 ◽  
Vol 116 (39) ◽  
pp. 19609-19618 ◽  
Author(s):  
Chenxi Tian ◽  
Karl R. Clauser ◽  
Daniel Öhlund ◽  
Steffen Rickelt ◽  
Ying Huang ◽  
...  
Keyword(s):  
Pancreatic Ductal Adenocarcinoma ◽  
Cancer Cells ◽  
Stromal Cells ◽  
Intraepithelial Neoplasia ◽  
Ductal Adenocarcinoma ◽  
Quantitative Mass Spectrometry ◽  
Chronic Pancreatitis Patient ◽  
Ecm Proteins ◽  
Poor Patient ◽  
Poor Patient Survival

Pancreatic ductal adenocarcinoma (PDAC) has prominent extracellular matrix (ECM) that compromises treatments yet cannot be nonselectively disrupted without adverse consequences. ECM of PDAC, despite the recognition of its importance, has not been comprehensively studied in patients. In this study, we used quantitative mass spectrometry (MS)-based proteomics to characterize ECM proteins in normal pancreas and pancreatic intraepithelial neoplasia (PanIN)- and PDAC-bearing pancreas from both human patients and mouse genetic models, as well as chronic pancreatitis patient samples. We describe detailed changes in both abundance and complexity of matrisome proteins in the course of PDAC progression. We reveal an early up-regulated group of matrisome proteins in PanIN, which are further up-regulated in PDAC, and we uncover notable similarities in matrix changes between pancreatitis and PDAC. We further assigned cellular origins to matrisome proteins by performing MS on multiple lines of human-to-mouse xenograft tumors. We found that, although stromal cells produce over 90% of the ECM mass, elevated levels of ECM proteins derived from the tumor cells, but not those produced exclusively by stromal cells, tend to correlate with poor patient survival. Furthermore, distinct pathways were implicated in regulating expression of matrisome proteins in cancer cells and stromal cells. We suggest that, rather than global suppression of ECM production, more precise ECM manipulations, such as targeting tumor-promoting ECM proteins and their regulators in cancer cells, could be more effective therapeutically.

scholarly journals Stomatin-like protein 2 is overexpressed in epithelial ovarian cancer and predicts poor patient survival

BMC Cancer ◽  
2015 ◽  
Vol 15 (1) ◽  
Author(s):  
Fei Sun ◽  
Wen Ding ◽  
Jie-Hua He ◽  
Xiao-Jing Wang ◽  
Ze-Biao Ma ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Epithelial Ovarian Cancer ◽  
Patient Survival ◽  
Poor Patient ◽  
Poor Patient Survival

scholarly journals Elevated expression of SATB1 is involved in pancreatic tumorigenesis and is associated with poor patient survival

2017 ◽  
Vol 16 (6) ◽  
pp. 8842-8848 ◽  
Author(s):  
Lei Guo ◽  
Jianjiang Zheng ◽  
Tao Yu ◽  
Yuequan Liu ◽  
Lukun Duo
Keyword(s):  
Patient Survival ◽  
Poor Patient ◽  
Elevated Expression ◽  
Poor Patient Survival

Lamins as cancer biomarkers

2010 ◽  
Vol 38 (1) ◽  
pp. 297-300 ◽  
Author(s):  
Clare R. Foster ◽  
Stefan A. Przyborski ◽  
Robert G. Wilson ◽  
Christopher J. Hutchison
Keyword(s):  
Cancer Cells ◽  
Patient Survival ◽  
Cancer Biomarkers ◽  
Tumour Cells ◽  
Diagnostic Biomarkers ◽  
Cancer Subtypes ◽  
Multifunctional Proteins ◽  
Poor Patient ◽  
Poor Patient Survival

Lamins are multifunctional proteins that are often aberrantly expressed or localized in tumours. Here, we endeavour to assess their uses as cancer biomarkers: to diagnose tumours, analyse cancer characteristics and predict patient survival. It appears that the nature of lamin function in cancer is very complex. Lamin expression can be variable between and even within cancer subtypes, which limits their uses as diagnostic biomarkers. Expression of A-type lamins is a marker of differentiated tumour cells and has been shown to be a marker of good or poor patient survival depending on tumour subtype. Further research into the functions of lamins in cancer cells and the mechanisms that determine its patterns of expression may provide more potential uses of lamins as cancer biomarkers.

scholarly journals The U2AF2 /circRNA ARF1/miR-342–3p/ISL2 feedback loop regulates angiogenesis in glioma stem cells

2020 ◽  
Vol 39 (1) ◽  
Author(s):  
Yang Jiang ◽  
Jinpeng Zhou ◽  
Junshuang Zhao ◽  
Haiying Zhang ◽  
Long Li ◽  
...  
Keyword(s):  
Stem Cells ◽  
Neural Development ◽  
Feedback Loop ◽  
Rna Binding ◽  
Patient Survival ◽  
Luciferase Reporter ◽  
Circular Rnas ◽  
Glioma Stem Cells ◽  
Poor Patient ◽  
Poor Patient Survival

Abstract Background Glioma is the most common and lethal primary brain tumor in adults, and angiogenesis is one of the key factors contributing to its proliferation, aggressiveness, and malignant transformation. However, the discovery of novel oncogenes and the study of its molecular regulating mechanism based on circular RNAs (circRNAs) may provide a promising treatment target in glioma. Methods Bioinformatics analysis, qPCR, western blotting, and immunohistochemistry were used to detect the expression levels of ISL2, miR-342–3p, circRNA ARF1 (cARF1), U2AF2, and VEGFA. Patient-derived glioma stem cells (GSCs) were established for the molecular experiments. Lentiviral-based infection was used to regulate the expression of these molecules in GSCs. The MTS, EDU, Transwell, and tube formation assays were used to detect the proliferation, invasion, and angiogenesis of human brain microvessel endothelial cells (hBMECs). RNA-binding protein immunoprecipitation, RNA pull-down, dual-luciferase reporter, and chromatin immunoprecipitation assays were used to detect the direct regulation mechanisms among these molecules. Results We first identified a novel transcription factor related to neural development. ISL2 was overexpressed in glioma and correlated with poor patient survival. ISL2 transcriptionally regulated VEGFA expression in GSCs and promoted the proliferation, invasion, and angiogenesis of hBMECs via VEGFA-mediated ERK signaling. Regarding its mechanism of action, cARF1 upregulated ISL2 expression in GSCs via miR-342–3p sponging. Furthermore, U2AF2 bound to and promoted the stability and expression of cARF1, while ISL2 induced the expression of U2AF2, which formed a feedback loop in GSCs. We also showed that both U2AF2 and cARF1 had an oncogenic effect, were overexpressed in glioma, and correlated with poor patient survival. Conclusions Our study identified a novel feedback loop among U2AF2, cARF1, miR-342–3p, and ISL2 in GSCs. This feedback loop promoted glioma angiogenesis, and could provide an effective biomarker for glioma diagnosis and prognostic evaluation, as well as possibly being used for targeted therapy.

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