USP5 promotes tumorigenesis and progression of pancreatic cancer by stabilizing FoxM1 protein

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.

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PD-1/PD-L1 expression in pancreatic cancer and its implication in novel therapies

Medicine and Pharmacy Reports ◽

10.15386/mpr-2116 ◽

2021 ◽

Author(s):

Adrian Mucileanu ◽

Romeo Chira ◽

Petru Adrian Mircea

Keyword(s):

Pancreatic Cancer ◽

T Cells ◽

Mismatch Repair ◽

Fluid Pressure ◽

Developed Countries ◽

Effector T Cells ◽

Desmoplastic Reaction ◽

Hypoxic Conditions ◽

Tumorigenesis And Progression ◽

High Level

Pancreatic cancer is the seventh leading cause of death in developed countries and it still has a poor prognosis despite intense research in the last 20 years. Immunotherapy is a relatively new strategy in cancer treatment. The aim of immunotherapy is to block the immunosuppressive effect of tumoral cells. The PD1/PD-L1 axis has an important role in the inhibition of effector T cells and the development of regulatory T cells (Tregs). Blocking these checkpoints, and also inhibitory signals, leads to apoptosis of Tregs and increased immune response of effector T cells against tumoral antigens. Unfortunately, pancreatic cancer is generally considered to be a non-immunogenic tumor. Thus PD-1/PD-L1 inhibitors demonstrated poor results in pancreatic cancer, excepting some patients with MSI/dMMR (microsatellite instability/deficient mismatch repair). Furthermore, pancreatic cancer has a particular microenvironment with a strong desmoplastic reaction, increased interstitial fluid pressure, hypoxic conditions, and acidic extracellular pH, which promote tumorigenesis and progression of the tumor. Mismatch repair deficiency (dMMR) is correlated with a high level of mutation-associated neoantigens, most recognized by immune cells which could predict a favorable response to anti-PD-1/PD-L1 therapy. PD-1/PD-L1 molecules could be also found as soluble forms (sPD-1, sPD-L1). These molecules have a potential role in the prognosis and treatment of pancreatic cancer.

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Activation of Vitamin D Receptor Signaling Downregulates the Expression of Nuclear FOXM1 Protein and Suppresses Pancreatic Cancer Cell Stemness

Clinical Cancer Research ◽

10.1158/1078-0432.ccr-14-2437 ◽

2014 ◽

Vol 21 (4) ◽

pp. 844-853 ◽

Cited By ~ 25

Author(s):

Zhiwei Li ◽

Zhiliang Jia ◽

Yong Gao ◽

Dacheng Xie ◽

Daoyan Wei ◽

...

Keyword(s):

Pancreatic Cancer ◽

Vitamin D ◽

Cancer Cell ◽

Vitamin D Receptor ◽

Pancreatic Cancer Cell ◽

Receptor Signaling ◽

Foxm1 Protein

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m6A-Mediated Upregulation of LINC00857 Promotes Pancreatic Cancer Tumorigenesis by Regulating the miR-150-5p/E2F3 Axis

Frontiers in Oncology ◽

10.3389/fonc.2021.629947 ◽

2021 ◽

Vol 11 ◽

Author(s):

Xiangrui Meng ◽

Yanyao Deng ◽

Shuhan He ◽

Li Niu ◽

Hongwei Zhu

Keyword(s):

Pancreatic Cancer ◽

Expression Profiling ◽

Rna Stability ◽

Regulatory Pathway ◽

Competing Endogenous Rna ◽

Mortality And Morbidity ◽

Interactive Analysis ◽

The Past ◽

Tumorigenesis And Progression ◽

Non Coding Rnas

The mortality and morbidity rates of pancreatic cancer (PC) have been increasing over the past two decades. Recent evidence indicates that long non-coding RNAs (lncRNAs) are usually dysregulated in the tumorigenesis and progression of PC. In the present study, we showed that the expression of LINC00857 was upregulated in PC and associated with poor prognosis based on the Gene Expression Profiling Interactive Analysis (GEPIA) database and validated in our PC tissues and cell lines. N6-Methyladenosine (m6A) was highly enriched within LINC00857 and enhanced its RNA stability. Knockdown of LINC00857 remarkably inhibited the proliferation and promoted the apoptosis of PC cells. Then, by using bioinformation analysis and verified experiments, we identified that LINC00857 functioned as a competing endogenous RNA (ceRNA) for sponging miR-150-5p, leading to the upregulation of its target E2F3 in PC cells. Taken above, our study revealed a potential ceRNA regulatory pathway in which LINC00857 modulates E2F3 expression by binding to miR-150-5p, ultimately promoting tumorigenesis in PC. LINC00857/miR-150-5p/E2F3 regulatory axis may be taken as an alternative therapeutic target for treating PC.

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Implications of HIF-1α in the tumorigenesis and progression of pancreatic cancer

Cancer Cell International ◽

10.1186/s12935-020-01370-0 ◽

2020 ◽

Vol 20 (1) ◽

Cited By ~ 4

Author(s):

Xiao Jin ◽

Lu Dai ◽

Yilan Ma ◽

Jiayan Wang ◽

Zheng Liu

Keyword(s):

Pancreatic Cancer ◽

Tumorigenesis And Progression

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

Journal of Oncology ◽

10.1155/2020/2845906 ◽

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.

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High Glucose-Induced ROS Production Stimulates Proliferation of Pancreatic Cancer via Inactivating the JNK Pathway

Oxidative Medicine and Cellular Longevity ◽

10.1155/2018/6917206 ◽

2018 ◽

Vol 2018 ◽

pp. 1-10 ◽

Cited By ~ 2

Author(s):

Jiao Luo ◽

Yukai Xiang ◽

Xiangxiang Xu ◽

Dazhang Fang ◽

Ding Li ◽

...

Keyword(s):

Pancreatic Cancer ◽

Cancer Cells ◽

High Glucose ◽

Ros Generation ◽

Cancer Cell Growth ◽

Jnk Pathway ◽

Pancreatic Cancer Cells ◽

Intracellular Ros ◽

Tumorigenesis And Progression

Aberrant glucose metabolism of diabetes mellitus or hyperglycemia stimulates pancreatic tumorigenesis and progression. Hyperglycemic environment can increase the ROS level of tumors, but the role of upregulation of ROS levels in pancreatic cancer (PC) still remains controversial. Here, the same as other reports, we demonstrate that high glucose promoted pancreatic cancer cell growth and resulted in an increase in the level of ROS. However, it is interesting that the phosphorylation of JNK was reduced. When treating PC cells with N-acetyl-L-cysteine (NAC), the intracellular ROS generation is repressed, but the expression of phosphorylation of JNK and c-Jun increased. Moreover, the JNK inhibitor SP600125 significantly promoted cell proliferation and suppressed cell apoptosis of pancreatic cancer cells under high glucose conditions. Collectively, high levels of ROS induced by high glucose conditions stimulated the proliferation of pancreatic cancer cells, and it may be achieved by inactivating the JNK pathway.

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Involvement of IL-4, IL-13 and Their Receptors in Pancreatic Cancer

International Journal of Molecular Sciences ◽

10.3390/ijms22062998 ◽

2021 ◽

Vol 22 (6) ◽

pp. 2998

Author(s):

Jingwei Shi ◽

Xujun Song ◽

Benno Traub ◽

Michael Luxenhofer ◽

Marko Kornmann

Keyword(s):

Pancreatic Cancer ◽

Immune Responses ◽

Structural Similarity ◽

Biological Properties ◽

Receptor Complex ◽

Type Ii ◽

Epithelial Tumor ◽

Wide Range ◽

Main Target ◽

Tumorigenesis And Progression

Interleukin (IL)-4 and IL-13 are known as pleiotropic Th2 cytokines with a wide range of biological properties and functions especially in immune responses. In addition, increasing activities have also been determined in oncogenesis and tumor progression of several malignancies. It is now generally accepted that IL-4 and IL-13 can exert effects on epithelial tumor cells through corresponding receptors. Type II IL-4 receptor (IL-4Rα/IL-13Rα1), predominantly expressed in non-hematopoietic cells, is identified to be the main target for both IL-4 and IL-13 in tumors. Moreover, IL-13 can also signal by binding to the IL-13Rα2 receptor. Structural similarity due to the use of the same receptor complex generated in response to IL-4/IL-13 results in overlapping but also distinct signaling pathways and functions. The aim of this review was to summarize knowledge about IL-4 and IL-13 and their receptors in pancreatic cancer in order understand the implication of IL-4 and IL-13 and their receptors for pancreatic tumorigenesis and progression and for developing possible new diagnostic and therapeutic targets.

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