scholarly journals Research Progress on Slit/Robo Pathway in Pancreatic Cancer: Emerging and Promising

2020 ◽  
Vol 2020 ◽  
pp. 1-7
Author(s):  
Cheng Ding ◽  
Yatong Li ◽  
Cheng Xing ◽  
Hanyu Zhang ◽  
Shunda Wang ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Signaling Pathway ◽  
Tumor Cells ◽  
Research Progress ◽  
Pathway Gene ◽  
Great Progress ◽  
Tumorigenesis And Progression ◽  
System Tumor ◽  
Signaling Pathway Gene

Pancreatic cancer is a highly malignant digestive system tumor which is the leading cause of cancer-related deaths. The basic and clinical research of pancreatic cancer has made great progress in recent years, and kinds of signaling pathways have been found in the tumorigenesis and progression in pancreatic cancer. The Slit glycoprotein (Slit) and Roundabout receptor (Robo) signaling pathway acts as a neural targeting factor with the axonal remnant, axon guidance, and inhibition of neuronal migration in the nervous system. In recent years, it has been found that the Slit/Robo signaling pathway has different degrees of expression changes in various tumor cells. In different tumor cells, the signaling pathway gene expression is different and regulates tumor angiogenesis, cell invasion, metastasis, and nerve infiltration. Herein, we summarize the mechanisms of the Slit/Robo pathway in the development and progression of pancreatic cancer, in order to have more understanding of the role of Slit/Robo in pancreatic cancer.

scholarly journals Long noncoding RNA 00976 promotes pancreatic cancer progression through OTUD7B by sponging miR-137 involving EGFR/MAPK pathway

2019 ◽  
Vol 38 (1) ◽  
Author(s):  
Shan Lei ◽  
Zhiwei He ◽  
Tengxiang Chen ◽  
Xingjun Guo ◽  
Zhirui Zeng ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Cell Proliferation ◽  
Signaling Pathway ◽  
Mapk Pathway ◽  
Mapk Signaling ◽  
Mapk Signaling Pathway ◽  
Migration And Invasion ◽  
Potential Biomarker

Abstract Background Accumulation evidence indicates the vital role of long non-coding RNAs (lncRNAs) in tumorigenesis and the progression of malignant tumors, including pancreatic cancer (PC). However, the role and the molecular mechanism of long non-coding RNA 00976 is unclear in pancreatic cancer. Methods In situ hybridization (ISH) and qRT-PCR was performed to investigate the association between linc00976 expression and the clinicopathological characteristics and prognosis of patients with PC. Subsequently, linc00976 over-expression vector and shRNAs were transfected into PC cells to up-regulate or down-regulate linc00976 expression. Loss- and gain-of function assays were performed to investigate the role of linc00976 in proliferation and metastasis in vitro and vivo. ITRAQ, bioinformatic analysis and rescue assay were used to illustrate the ceRNA mechanism network of linc00976/miR-137/OTUD7B and its downstream EGFR/MAPK signaling pathway. Results linc00976 expression was overexpressed in PC tissues and cell lines and was positively associated with poorer survival in patients with PC. Function studies revealed that linc00976 knockdown significantly suppressed cell proliferation, migration and invasion in vivo and in vitro, whereas its overexpression reversed these effects. Based on Itraq results and online database prediction, Ovarian tumor proteases OTUD7B was found as a downstream gene of linc00976, which deubiquitinated EGFR mediates MAPK signaling activation. Furthermore, Bioinformatics analysis and luciferase assays and rescue experiments revealed that linc00976/miR137/OTUD7B established the ceRNA network modulating PC cell proliferation and tumor growth. Conclusion The present study demonstrates that linc00976 enhances the proliferation and invasion ability of PC cells by upregulating OTUD7B expression, which was a target of miR-137. Ultimately, OTUD7B mediates EGFR and MAPK signaling pathway, suggesting that linc00976/miR-137/OTUD7B/EGFR axis may act as a potential biomarker and therapeutic target for PC.

scholarly journals The critical role and potential target of the autotaxin/lysophosphatidate axis in pancreatic cancer

Tumor Biology ◽  
2017 ◽  
Vol 39 (3) ◽  
pp. 101042831769454 ◽  
Author(s):  
Ming Quan ◽  
Jiu-jie Cui ◽  
Xiao Feng ◽  
Qian Huang
Keyword(s):  
Pancreatic Cancer ◽  
Current Knowledge ◽  
Critical Role ◽  
Treatment Resistance ◽  
G Protein Coupled Receptors ◽  
Signaling Axis ◽  
Tumorigenesis And Progression ◽  
Pathologic Processes ◽  
G Protein Coupled

Autotaxin, an ecto-lysophospholipase D encoded by the human ENNP2 gene, is expressed in multiple tissues, and participates in numerous critical physiologic and pathologic processes including inflammation, pain, obesity, embryo development, and cancer via the generation of the bioactive lipid lysophosphatidate. Overwhelming evidences indicate that the autotaxin/lysophosphatidate signaling axis serves key roles in the numerous processes central to tumorigenesis and progression, including proliferation, survival, migration, invasion, metastasis, cancer stem cell, tumor microenvironment, and treatment resistance by interacting with a series of at least six G-protein-coupled receptors (LPAR1–6). This review provides an overview of the autotaxin/lysophosphatidate axis and collates current knowledge regarding its specific role in pancreatic cancer. With a deeper understanding of the critical role of the autotaxin/lysophosphatidate axis in pancreatic cancer, targeting autotaxin or lysophosphatidate receptor may be a potential and promising strategy for cancer therapy.

TGFbeta-BMP signaling pathway gene expression in osteoporotic postmenopausal women by DNA microarrays

Bone ◽  
2011 ◽  
Vol 48 ◽  
pp. S159
Author(s):  
T. Koromila ◽  
Z. Dailiana ◽  
S. Samara ◽  
C. Chassanidis ◽  
V. Aleporou - Marinou ◽  
...  
Keyword(s):  
Gene Expression ◽  
Postmenopausal Women ◽  
Signaling Pathway ◽  
Dna Microarrays ◽  
Bmp Signaling ◽  
Pathway Gene ◽  
Signaling Pathway Gene

scholarly journals The Role of Microtubules in Pancreatic Cancer: Therapeutic Progress

2021 ◽  
Vol 11 ◽  
Author(s):  
Mugahed Abdullah Hasan Albahde ◽  
Bulat Abdrakhimov ◽  
Guo-Qi Li ◽  
Xiaohu Zhou ◽  
Dongkai Zhou ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Cell Division ◽  
Pancreatic Carcinoma ◽  
Cancer Cells ◽  
Tumor Cells ◽  
Cytoskeletal Proteins ◽  
Late Diagnosis ◽  
Apoptosis Induction ◽  
Microtubule Targeting Agents

Pancreatic cancer has an extremely low prognosis, which is attributable to its high aggressiveness, invasiveness, late diagnosis, and lack of effective therapies. Among all the drugs joining the fight against this type of cancer, microtubule-targeting agents are considered to be the most promising. They inhibit cancer cells although through different mechanisms such as blocking cell division, apoptosis induction, etc. Hereby, we review the functions of microtubule cytoskeletal proteins in tumor cells and comprehensively examine the effects of microtubule-targeting agents on pancreatic carcinoma.

scholarly journals Activation of the NF-κB Signaling Pathway Promotes Malignancy in Bladder Cancer Cells in a Positive Feedback Manner

2020 ◽  
Author(s):  
Zhenfeng guan ◽  
Yi Sun ◽  
YaZhuo Jiang ◽  
Xinyang Wang ◽  
Jinhai Fan
Keyword(s):  
Bladder Cancer ◽  
Endothelial Cells ◽  
Tumor Cell ◽  
Tumor Progression ◽  
Signaling Pathway ◽  
Tumor Cells ◽  
Positive Feedback ◽  
Umbilical Vein

Abstract Background: The main issue arising from bladder cancer (BCa) is the high relapse ratio and tumor progression, the mechanism of which remains to be elucidated. Interaction of tumor cells with the stroma of microenvironment promoting tumor progression warrants much attention from researchers. Among all stromal cells, endothelial cells (ECs) are exceptional. Numerous studies have investigated its role of angiogenesis, but have not studied immunocyte recruitment and chemokine secretion, the important significance of which in tumor progression has been proven. Meanwhile, to the best of our knowledge, few studies have focused on the direct interaction between tumor cells and ECs in BCa tissue, which was the aim of the present study. Methods: In the present study, immunohistochemical staining is used for detecting the distribution of ECs in BCa tissue, and we use SPSS 19 to analysis the relationship between ECs distribution and tumor grade/stage; inadition, co-curlturing of tumor cell with ECs is usd to mimicking the interaction of tumor cell with ECs, followed by Chamber Assay, BrdU incorporoartion, WB, Qt-PCR, ect, to investiatin the mechanism. Results: The distribution of ECs in BCa tissue is significantly increased according to BCa grade and negatively associated to the time from BCa diagnosis to progression, manifesting as an independent risk factor for BCa prognosis. The following in vitro experiment indicates that the conditional medium from co-culture of tumor cells (T24/J82) with ECs (human umbilical vein endothelial cells, which were used as ECs in the in vitro experiment) contributes to the activation of the NF-ĸB signaling pathway in tumor cells, leading to the upregulation of CXCL1/8. This further results in enhanced tumor cell malignancy and EC recruitment, manifested as a positive feedback loop. Conclusions: The present study provided a further understanding on the role of ECs in BCa progression—not only by angiogenesis but also by interacting with tumor cell dirctly.

scholarly journals Growth Hormone Receptor Inhibition Sensitizes Human Pancreatic Cancer to Chemotherapy Treatments

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. A1019-A1020
Author(s):  
Reetobrata Basu ◽  
John Joseph Kopchick ◽  
Silvana Duran Ortiz ◽  
Yanrong Qian ◽  
Prateek Kulkarni
Keyword(s):  
Pancreatic Cancer ◽  
Growth Hormone ◽  
Cancer Cells ◽  
Tumor Cells ◽  
Hormone Receptor ◽  
Growth Hormone Receptor ◽  
Human Pancreatic Cancer ◽  
Drug Efflux ◽  
Pancreatic Cancer Cells

Abstract Human growth hormone (GH) and its cognate growth hormone receptor (GHR) have been established to have a distinct role in promoting the progression of several types of human cancers. We had earlier described a newfound role of the GH-GHR axis in driving chemoresistance in melanoma by upregulating drug efflux by ABC multidrug transporter expression and a phenotype switch by induction of epithelial-to-mesenchymal transition (EMT). Here we present an in-depth analysis of this role of GH-GHR in the highly therapy resistant human pancreatic cancer which has a 5-year survival rate of only 10% in 2020. Using human and mouse pancreatic cancer cells and RNA and protein expression analyses by RT-qPCR, ELISA, and western-blot, we identified that (i) GH upregulates specific ABC-transporter expressions in a drug-context specific manner, (ii) GH upregulates EMT transcription factors, (iii) GH activates specific oncogenic signaling pathways, and (iii) GH action increases cytochrome P450 members involved in hepatic drug metabolism. The GH antagonist, Pegvisomant, significantly inhibited these effects. Additionally, we confirmed the effects of these molecular changes by specific assays. For example, GH increases basement membrane invasion, viability of circulating tumor cells, and drug efflux; while inhibition of GHR by pegvisomant in pancreatic cancer cells reversed this aggressive tumor phenotype and sensitized the tumor cells to chemotherapy. Cell viability assays confirmed a decreased IC50 of gemcitabine, doxorubicin, and erlotinib in pancreatic cancer cells treated with pegvisomant and an increase in IC50 cells treated with GH. We further verified our results using in silico analyses of TCGA datasets for pancreatic cancer - which provided robust confirmation of our experimental findings. Presently we are validating our observation in nude mice with human pancreatic cancer cell xenografts. In conclusion, our in vitro results confirm that GHR antagonism can drastically sensitize human pancreatic cancer cells by blocking mechanisms of drug resistance, thus providing a valuable window for improved efficacy of available chemo- and targeted therapy.

The preliminary role of circulating tumor cells obtained from the hepatic or portal veins in patients with hepatobiliary–pancreatic cancer

2016 ◽  
Vol 49 (1) ◽  
pp. 5-8
Author(s):  
Naokazu Chiba ◽  
Yuta Abe ◽  
Yosuke Ozawa ◽  
Kosuke Hikita ◽  
Masaaki Okihara ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Tumor Cells ◽  
Circulating Tumor Cells ◽  
Portal Veins
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