scholarly journals Folded and Unfolded Conformations of Proteins Involved in Pancreatic Cancer: a Layman's Guide

2010 ◽  
Vol 10 ◽  
pp. 1612-1633 ◽  
Author(s):  
Jerónimo Bravo ◽  
José L. Neira
Keyword(s):  
Pancreatic Cancer ◽  
Amino Acids ◽  
Signaling Pathways ◽  
Cancer Progression ◽  
Current Knowledge ◽  
Biochemical Pathway ◽  
Natively Unfolded ◽  
Folded Proteins ◽  
Key Residues ◽  
Hub Proteins

Pancreatic cancer (PC) is one of the most difficult illnesses to treat, since the 5-year survival rate is lower than 5% in patients and no substantial advances in its treatment have been achieved in the last 20 years. Since cancer deregulation and progression are associated with changes in at least one biochemical pathway, the knowledge of the structure of the proteins involved in such routes seems to be crucial in order to understand how this cancer progresses and, more importantly, to design more efficient and rationally designed drugs. In this review, we describe the fold and structures of proteins involved in different signaling pathways that intervene during PC development and progression. In particular, we will focus on the most frequently mutated, or alternatively differently expressed, proteins in PC. The current knowledge suggests that most of the proteins carry out their function by interacting with others via specific domains and through key residues at the recognition interfaces; these amino acids are mutated in patients developing PC. Furthermore, phosphorylation seems to be a crucial regulation step along several signaling pathways. Finally, we show not only that well-folded proteins in several signaling pathways are critical in the development of PC, but also that natively unfolded “hub” proteins, able to interact with DNA or proteins, are also important in such cancer progression.

scholarly journals miR-1266 Contributes to Pancreatic Cancer Progression and Chemoresistance by the STAT3 and NF-κB Signaling Pathways

2018 ◽  
Vol 11 ◽  
pp. 142-158 ◽  
Author(s):  
Xin Zhang ◽  
Dong Ren ◽  
Xianqiu Wu ◽  
Xi Lin ◽  
Liping Ye ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Signaling Pathways ◽  
Cancer Progression

scholarly journals Crosstalk between the canonical NF-κB and Notch signaling pathways inhibits Pparγ expression and promotes pancreatic cancer progression in mice

2011 ◽  
Vol 121 (12) ◽  
pp. 4685-4699 ◽  
Author(s):  
Eleni Maniati ◽  
Maud Bossard ◽  
Natalie Cook ◽  
Juliana B. Candido ◽  
Nia Emami-Shahri ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Notch Signaling ◽  
Signaling Pathways ◽  
Cancer Progression ◽  
Pparγ Expression

scholarly journals Elucidating the Role of Extracellular Vesicles in Pancreatic Cancer

Cancers ◽  
2021 ◽  
Vol 13 (22) ◽  
pp. 5669
Author(s):  
Akbar Lulu Marzan ◽  
Sarah Elizabeth Stewart
Keyword(s):  
Drug Delivery ◽  
Pancreatic Cancer ◽  
Survival Rate ◽  
Extracellular Vesicles ◽  
Cancer Progression ◽  
Current Knowledge ◽  
Treatment Options ◽  
Metabolic Dysfunction ◽  
Underlying Mechanisms

Pancreatic cancer is one of the deadliest cancers worldwide, with a 5-year survival rate of less than 10%. This dismal survival rate can be attributed to several factors including insufficient diagnostics, rapid metastasis and chemoresistance. To identify new treatment options for improved patient outcomes, it is crucial to investigate the underlying mechanisms that contribute to pancreatic cancer progression. Accumulating evidence suggests that extracellular vesicles, including exosomes and microvesicles, are critical players in pancreatic cancer progression and chemoresistance. In addition, extracellular vesicles also have the potential to serve as promising biomarkers, therapeutic targets and drug delivery tools for the treatment of pancreatic cancer. In this review, we aim to summarise the current knowledge on the role of extracellular vesicles in pancreatic cancer progression, metastasis, immunity, metabolic dysfunction and chemoresistance, and discuss their potential roles as biomarkers for early diagnosis and drug delivery vehicles for treatment of pancreatic cancer.

scholarly journals S100 Proteins in Pancreatic Cancer: Current Knowledge and Future Perspectives

2021 ◽  
Vol 11 ◽  
Author(s):  
Yu Wu ◽  
Qi Zhou ◽  
Fangyue Guo ◽  
Mingming Chen ◽  
Xufeng Tao ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Cancer Progression ◽  
Calcium Binding ◽  
Current Knowledge ◽  
S100 Protein ◽  
Structural Similarity ◽  
Enzyme Activation ◽  
S100 Proteins ◽  
Effective Interventions ◽  
Vital Functions

Pancreatic cancer (PC) is a highly malignant tumor occurring in the digestive system. Currently, there is a lack of specific and effective interventions for PC; thus, further exploration regarding the pathogenesis of this malignancy is warranted. The S100 protein family, a collection of calcium-binding proteins expressed only in vertebrates, comprises 25 members with high sequence and structural similarity. Dysregulated expression of S100 proteins is a biomarker of cancer progression and prognosis. Functionally, these proteins are associated with the regulation of multiple cellular processes, including proliferation, apoptosis, growth, differentiation, enzyme activation, migration/invasion, Ca2+ homeostasis, and energy metabolism. This review highlights the significance of the S100 family in the diagnosis and prognosis of PC and its vital functions in tumor cell metastasis, invasion and proliferation. A further understanding of S100 proteins will provide potential therapeutic targets for preventing or treating PC.

scholarly journals Mechanism of Apoptosis Induced by Curcumin in Colorectal Cancer

2019 ◽  
Vol 20 (10) ◽  
pp. 2454 ◽  
Author(s):  
Nor Isnida Ismail ◽  
Iekhsan Othman ◽  
Faridah Abas ◽  
Nordin H. Lajis ◽  
Rakesh Naidu
Keyword(s):  
Colorectal Cancer ◽  
Side Effects ◽  
Signaling Pathways ◽  
Cancer Progression ◽  
Current Knowledge ◽  
Current Treatment ◽  
Treatment Modalities ◽  
Ancient Medicine ◽  
Colorectal Cancer Progression ◽  
Apoptosis Regulation

Colorectal cancer (CRC) is among the top three cancer with higher incident and mortality rate worldwide. It is estimated that about over than 1.1 million of death and 2.2 million new cases by the year 2030. The current treatment modalities with the usage of chemo drugs such as FOLFOX and FOLFIRI, surgery and radiotherapy, which are usually accompanied with major side effects, are rarely cured along with poor survival rate and at higher recurrence outcome. This trigger the needs of exploring new natural compounds with anti-cancer properties which possess fewer side effects. Curcumin, a common spice used in ancient medicine was found to induce apoptosis by targeting various molecules and signaling pathways involved in CRC. Disruption of the homeostatic balance between cell proliferation and apoptosis could be one of the promoting factors in colorectal cancer progression. In this review, we describe the current knowledge of apoptosis regulation by curcumin in CRC with regard to molecular targets and associated signaling pathways.

Study of metabolic reprogramming during pancreatic cancer progression: Metabolism of branched chain amino acids

Pancreatology ◽  
2017 ◽  
Vol 17 (3) ◽  
pp. S114-S115
Author(s):  
Victoire Gouirand ◽  
Q. Da Costa ◽  
G. Bidaut ◽  
S. Beloribi-Djefaflia ◽  
T. Gicquel ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Amino Acids ◽  
Cancer Progression ◽  
Branched Chain Amino Acids ◽  
Metabolic Reprogramming ◽  
Branched Chain

Molecular Docking Analysis of Flavonoid Compounds with Matrix Metalloproteinase-8 for the Identification of Potential Effective Inhibitors

2020 ◽  
Vol 17 ◽  
Author(s):  
Amir Taherkhani ◽  
Athena Orangi ◽  
Shirin Moradkhani ◽  
Zahra Khamverdi
Keyword(s):  
Amino Acids ◽  
Molecular Docking ◽  
Amino Acid ◽  
Matrix Metalloproteinase ◽  
Ligand Binding ◽  
Chronic Inflammation ◽  
Cancer Progression ◽  
Dimensional Structure ◽  
Control Test ◽  
Therapeutic Procedures

Background: Matrix metalloproteinase-8 (MMP-8) participates in degradation of different types of collagens in the extracellular matrix and basement membrane. Up-regulation of the MMP-8 has been demonstrated in many of disorders including cancer development, tooth caries, periodontal/peri-implant soft and hard tissue degeneration, and acute/chronic inflammation. Therefore, MMP-8 has become an encouraging target for therapeutic procedures for scientists. We carried out molecular docking approach to study the binding affinity of 29 flavonoids, as drug candidates, with the MMP-8. Pharmacokinetic and toxicological properties of the compounds were also studied. Moreover, it was attempted to identify the most important amino acids participating in ligand binding based on degree of each of the amino acids in the ligand-amino acid interaction network for MMP-8. Methods: Three-dimensional structure of the protein was gained from the RCSB database (PDB ID: 4QKZ). AutoDock version 4.0 and Cytoscape 3.7.2 were used for molecular docking and network analysis, respectively. Notably, the inhibitor of the protein in the crystalline structure of the 4QKZ was considered as a control test. Pharmacokinetic and toxicological features of compounds were predicted using bioinformatic web tools. Post-docking analyses were performed using BIOVIA Discovery Studio Visualizer version 19.1.0.18287. Results and Discussions: According to results, 24 of the studied compounds considered to be top potential inhibitors for MMP-8 based on their salient estimated free energy of binding and inhibition constant as compared with the control test: Apigenin-7-glucoside, nicotiflorin, luteolin, glabridin, taxifolin, apigenin, licochalcone A, quercetin, isorhamnetin, myricetin, herbacetin, kaemferol, epicatechin, chrysin, amentoflavone, rutin, orientin, epiafzelechin, quercetin-3-rhamnoside, formononetin, isoliquiritigenin, vitexin, catechine, isoquercitrin. Moreover, His-197 was found to be the most important amino acid involved in the ligand binding for the enzyme. Conclusion: The results of the current study could be used in the prevention and therapeutic procedures of a number of disorders such as cancer progression and invasion, oral diseases, and acute/chronic inflammation. Although, in vitro and in vivo tests are inevitable in the future.

scholarly journals Bone morphogenetic proteins, breast cancer, and bone metastases: striking the right balance

2017 ◽  
Vol 24 (10) ◽  
pp. R349-R366 ◽  
Author(s):  
Catherine Zabkiewicz ◽  
Jeyna Resaul ◽  
Rachel Hargest ◽  
Wen Guo Jiang ◽  
Lin Ye
Keyword(s):  
Breast Cancer ◽  
Cancer Progression ◽  
Bone Morphogenetic Proteins ◽  
Therapeutic Potential ◽  
Current Knowledge ◽  
Breast Tumour ◽  
Cellular Functions ◽  
Foetal Development ◽  
Key Factor ◽  
The Right

Bone morphogenetic proteins (BMPs) belong to the TGF-β super family, and are essential for the regulation of foetal development, tissue differentiation and homeostasis and a multitude of cellular functions. Naturally, this has led to the exploration of aberrance in this highly regulated system as a key factor in tumourigenesis. Originally identified for their role in osteogenesis and bone turnover, attention has been turned to the potential role of BMPs in tumour metastases to, and progression within, the bone niche. This is particularly pertinent to breast cancer, which commonly metastasises to bone, and in which studies have revealed aberrations of both BMP expression and signalling, which correlate clinically with breast cancer progression. Ultimately a BMP profile could provide new prognostic disease markers. As the evidence suggests a role for BMPs in regulating breast tumour cellular function, in particular interactions with tumour stroma and the bone metastatic microenvironment, there may be novel therapeutic potential in targeting BMP signalling in breast cancer. This review provides an update on the current knowledge of BMP abnormalities and their implication in the development and progression of breast cancer, particularly in the disease-specific bone metastasis.

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