scholarly journals Inflammation and tumor progression: signaling pathways and targeted intervention

2021 ◽  
Vol 6 (1) ◽  
Author(s):  
Huakan Zhao ◽  
Lei Wu ◽  
Guifang Yan ◽  
Yu Chen ◽  
Mingyue Zhou ◽  
...  
Keyword(s):  
Growth Factor ◽  
Tumor Progression ◽  
Signaling Pathways ◽  
Transforming Growth Factor ◽  
Response To Therapy ◽  
Janus Kinase ◽  
Oncolytic Viruses ◽  
Mitogen Activated Protein Kinase ◽  
Resolution Of Inflammation ◽  
Chemokine Ligands

AbstractCancer development and its response to therapy are regulated by inflammation, which either promotes or suppresses tumor progression, potentially displaying opposing effects on therapeutic outcomes. Chronic inflammation facilitates tumor progression and treatment resistance, whereas induction of acute inflammatory reactions often stimulates the maturation of dendritic cells (DCs) and antigen presentation, leading to anti-tumor immune responses. In addition, multiple signaling pathways, such as nuclear factor kappa B (NF-kB), Janus kinase/signal transducers and activators of transcription (JAK-STAT), toll-like receptor (TLR) pathways, cGAS/STING, and mitogen-activated protein kinase (MAPK); inflammatory factors, including cytokines (e.g., interleukin (IL), interferon (IFN), and tumor necrosis factor (TNF)-α), chemokines (e.g., C-C motif chemokine ligands (CCLs) and C-X-C motif chemokine ligands (CXCLs)), growth factors (e.g., vascular endothelial growth factor (VEGF), transforming growth factor (TGF)-β), and inflammasome; as well as inflammatory metabolites including prostaglandins, leukotrienes, thromboxane, and specialized proresolving mediators (SPM), have been identified as pivotal regulators of the initiation and resolution of inflammation. Nowadays, local irradiation, recombinant cytokines, neutralizing antibodies, small-molecule inhibitors, DC vaccines, oncolytic viruses, TLR agonists, and SPM have been developed to specifically modulate inflammation in cancer therapy, with some of these factors already undergoing clinical trials. Herein, we discuss the initiation and resolution of inflammation, the crosstalk between tumor development and inflammatory processes. We also highlight potential targets for harnessing inflammation in the treatment of cancer.

scholarly journals Signaling pathways in cancer-associated fibroblasts and targeted therapy for cancer

2021 ◽  
Vol 6 (1) ◽  
Author(s):  
Fanglong Wu ◽  
Jin Yang ◽  
Junjiang Liu ◽  
Ye Wang ◽  
Jingtian Mu ◽  
...  
Keyword(s):  
Growth Factor ◽  
Cancer Cells ◽  
Signaling Pathways ◽  
Cancer Progression ◽  
Transforming Growth Factor Beta ◽  
Transforming Growth Factor ◽  
Janus Kinase ◽  
Mitogen Activated Protein Kinase ◽  
Matrix Remodeling ◽  
Cancer Associated Fibroblasts

AbstractTo flourish, cancers greatly depend on their surrounding tumor microenvironment (TME), and cancer-associated fibroblasts (CAFs) in TME are critical for cancer occurrence and progression because of their versatile roles in extracellular matrix remodeling, maintenance of stemness, blood vessel formation, modulation of tumor metabolism, immune response, and promotion of cancer cell proliferation, migration, invasion, and therapeutic resistance. CAFs are highly heterogeneous stromal cells and their crosstalk with cancer cells is mediated by a complex and intricate signaling network consisting of transforming growth factor-beta, phosphoinositide 3-kinase/AKT/mammalian target of rapamycin, mitogen-activated protein kinase, Wnt, Janus kinase/signal transducers and activators of transcription, epidermal growth factor receptor, Hippo, and nuclear factor kappa-light-chain-enhancer of activated B cells, etc., signaling pathways. These signals in CAFs exhibit their own special characteristics during the cancer progression and have the potential to be targeted for anticancer therapy. Therefore, a comprehensive understanding of these signaling cascades in interactions between cancer cells and CAFs is necessary to fully realize the pivotal roles of CAFs in cancers. Herein, in this review, we will summarize the enormous amounts of findings on the signals mediating crosstalk of CAFs with cancer cells and its related targets or trials. Further, we hypothesize three potential targeting strategies, including, namely, epithelial–mesenchymal common targets, sequential target perturbation, and crosstalk-directed signaling targets, paving the way for CAF-directed or host cell-directed antitumor therapy.

scholarly journals Cripto-1 Activates Nodal- and ALK4-Dependent and -Independent Signaling Pathways in Mammary Epithelial Cells

2002 ◽  
Vol 22 (8) ◽  
pp. 2586-2597 ◽  
Author(s):  
Caterina Bianco ◽  
Heather B. Adkins ◽  
Christian Wechselberger ◽  
Masaharu Seno ◽  
Nicola Normanno ◽  
...  
Keyword(s):  
Mammary Gland ◽  
Growth Factor ◽  
Epithelial Cells ◽  
Signaling Pathways ◽  
Family Member ◽  
Transforming Growth Factor ◽  
Mammary Epithelial Cells ◽  
Mammary Epithelial ◽  
Mitogen Activated Protein Kinase ◽  
Type I

ABSTRACT Cripto-1 (CR-1), an epidermal growth factor-CFC (EGF-CFC) family member, has a demonstrated role in embryogenesis and mammary gland development and is overexpressed in several human tumors. Recently, EGF-CFC proteins were implicated as essential signaling cofactors for Nodal, a transforming growth factor β family member whose expression has previously been defined as embryo specific. To identify a receptor for CR-1, a human brain cDNA phage display library was screened using CR-1 protein as bait. Phage inserts with identity to ALK4, a type I serine/threonine kinase receptor for Activin, were identified. CR-1 binds to cell surface ALK4 expressed on mammalian epithelial cells in fluorescence-activated cell sorter analysis, as well as by coimmunoprecipitation. Nodal is coexpressed with mouse Cr-1 in the mammary gland, and CR-1 can phosphorylate the transcription factor Smad-2 in EpH-4 mammary epithelial cells only in the presence of Nodal and ALK4. In contrast, CR-1 stimulation of mitogen-activated protein kinase and AKT in these cells is independent of Nodal and ALK4, suggesting that CR-1 may modulate different signaling pathways to mediate its different functional roles.

Trace of Long non-coding RNAs in Signaling Pathways Relative to Thyroid Cancer

2020 ◽  
Vol 15 ◽  
Author(s):  
Mohsen Safaei ◽  
Ameneh Mehri-Ghahfarrokhi ◽  
Ali Shojaeian
Keyword(s):  
Thyroid Cancer ◽  
Signaling Pathways ◽  
Messenger Rna ◽  
Transforming Growth Factor ◽  
Janus Kinase ◽  
Mitogen Activated Protein Kinase ◽  
Tumor Promoter ◽  
Mesenchymal Transition ◽  
Open Access Journals ◽  
Micro Rnas

Background: Long non-coding ribonucleic acid (lncRNA) is known as similar transcripts of messenger RNA (mRNA) whose size discrepancy is between 100 and 200 nucleotides. Recent studies in this area have revealed that lncRNAs are involved in cancer tumorogenesis and progression. Such molecules are transcribed from genome regions that lack open reading frame (ORF) and fail to encode any protein. LncRNAs are characterized by tumorigenic behaviors which can be considered as new biomarkers. Among all types of thyroid cancer (TC), papillary thyroid carcinoma (PTC) is the most common one. Methods: This review was prepared via searching of the databases of Science Direct, Directory of Open Access Journals (DOAJ), Google Scholar, Pub-Med (NLM), Scopus, Web of Science, and hand searching using relative keywords. The selected papers were fully reviewed and required information for the review was extracted and summarized. Results: Pervious studies indicated that BRAF-activated non-protein coding RNA (BANCR) expression had been increased in thyroid tumors compared with adjacent normal tissues. Additionally, BANCR had mediated epithelial-mesenchymal transition (EMT) through regulating the expression of epithelial (E)-cadherin, vimentin, and neuronal (N)-cadherin. Moreover, H19 was an example of an lncRNA that could function either as a tumor promoter or suppressor. An important part of this study was dedicated to reviewing signaling pathways involved in TC including extracellular-signal-regulated kinase (ERK) pathway and mitogen-activated protein kinase (ERK/MAPK), transforming growth factor-β/ (TGF-ß)/Smads, the Janus kinase/signal transducers and activators of transcription (JAK/STAT), P53, as well as other pathways. Conclusion: Briefly, this study provided an overview on current understanding of the function of lncRNA and micro RNAs (miRNAs) along with their interactions in TC.

scholarly journals Exploring major signaling cascades in melanomagenesis: a rationale route for targetted skin cancer therapy

2018 ◽  
Vol 38 (5) ◽  
Author(s):  
Paola M. Dantonio ◽  
Marianne O. Klein ◽  
Maria Renata V.B. Freire ◽  
Camila N. Araujo ◽  
Ana Carolina Chiacetti ◽  
...  
Keyword(s):  
Signaling Pathways ◽  
Transforming Growth Factor ◽  
Survival Rates ◽  
Transforming Growth Factor Β ◽  
Janus Kinase ◽  
Mitogen Activated Protein Kinase ◽  
Signaling Cascades ◽  
Mitogen Activated Protein ◽  
Metastatic Sites ◽  
The Impact

Although most melanoma cases may be treated by surgical intervention upon early diagnosis, a significant portion of patients can still be refractory, presenting low survival rates within 5 years after the discovery of the illness. As a hallmark, melanomas are highly prone to evolve into metastatic sites. Moreover, melanoma tumors are highly resistant to most available drug therapies and their incidence have increased over the years, therefore leading to public health concerns about the development of novel therapies. Therefore, researches are getting deeper in unveiling the mechanisms by which melanoma initiation can be triggered and sustained. In this context, important progress has been achieved regarding the roles and the impact of cellular signaling pathways in melanoma. This knowledge has provided tools for the development of therapies based on the intervention of signal(s) promoted by these cascades. In this review, we summarize the importance of major signaling pathways (mitogen-activated protein kinase (MAPK), phosphoinositide 3-kinase (PI3K)-Akt, Wnt, nuclear factor κ-light-chain-enhancer of activated B cell (NF-κB), Janus kinase (JAK)-signal transducer and activator of transcription (STAT), transforming growth factor β (TGF-β) and Notch) in skin homeostasis and melanoma progression. Available and developing melanoma therapies interfering with these signaling cascades are further discussed.

scholarly journals Signaling pathways of EBV-induced oncogenesis

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Yin Luo ◽  
Yitong Liu ◽  
Chengkun Wang ◽  
Runliang Gan
Keyword(s):  
Protein Kinase ◽  
Signaling Pathways ◽  
Noncoding Rna ◽  
Transforming Growth Factor ◽  
Transforming Growth Factor Β ◽  
Nuclear Factor Κb ◽  
Janus Kinase ◽  
Mitogen Activated Protein Kinase ◽  
Transcription Activator ◽  
Barr Virus

AbstractEpstein-Barr virus (EBV) is closely associated with multiple human cancers. EBV-associated cancers are mainly lymphomas derived from B cells and T cells (Hodgkin lymphoma, Burkitt lymphoma, NK/T-cell lymphoma, and posttransplant lymphoproliferative disorder (PTLD)) and carcinomas derived from epithelial cells (nasopharyngeal carcinoma and gastric carcinoma). EBV can induce oncogenesis in its host cell by activating various signaling pathways, such as nuclear factor-κB (NF-κB), phosphoinositide-3-kinase/protein kinase B (PI3K/AKT), Janus kinase/signal transducer and transcription activator (JAK/STAT), mitogen-activated protein kinase (MAPK), transforming growth factor-β (TGF-β), and Wnt/β-catenin, which are regulated by EBV-encoded proteins and noncoding RNA. In this review, we focus on the oncogenic roles of EBV that are mediated through the aforementioned signaling pathways.

scholarly journals Signaling pathways involved in colorectal cancer progression

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Zahra Koveitypour ◽  
Farnoush Panahi ◽  
Mehrdad Vakilian ◽  
Maryam Peymani ◽  
Farzad Seyed Forootan ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Growth Factor ◽  
Signaling Pathways ◽  
Cancer Progression ◽  
Molecular Mechanisms ◽  
Transforming Growth Factor ◽  
Growth Factor Receptor ◽  
Transforming Growth Factor Β ◽  
Mitogen Activated Protein Kinase ◽  
Mapk Cascades

AbstractColorectal cancer (CRC) is the fourth leading cause of the worldwide cancer mortality. Different molecular mechanisms have been attributed to the development and progress of CRC. In this review, we will focus on the mitogen-activated protein kinase (MAPK) cascades downstream of the epidermal growth factor receptor (EGFR), Notch, PI3K/AKT pathway, transforming growth factor-β (TGF-β), and Wnt signaling pathways. Various mutations in the components of these signaling pathways have been linked to the development of CRC. Accordingly, numerous efforts have been carried out to target the signaling pathways to develop novel therapeutic approaches. Herein, we review the signaling pathways involved in the incidence and progression of CRC, and the strategies for the therapy targeting components of signaling pathways in CRC.

scholarly journals MicroRNAs in Transforming Growth Factor-Beta Signaling Pathway Associated With Fibrosis Involving Different Systems of the Human Body

2021 ◽  
Vol 8 ◽  
Author(s):  
Xiaoyang Xu ◽  
Pengyu Hong ◽  
Zhefu Wang ◽  
Zhangui Tang ◽  
Kun Li
Keyword(s):  
Growth Factor ◽  
Signaling Pathways ◽  
Signaling Pathway ◽  
Human Body ◽  
Transforming Growth Factor Beta ◽  
Transforming Growth Factor ◽  
Coiled Coil ◽  
Janus Kinase ◽  
Future Research ◽  
Growth Factor Beta

Fibrosis, a major cause of morbidity and mortality, is a histopathological manifestation of many chronic inflammatory diseases affecting different systems of the human body. Two types of transforming growth factor beta (TGF-β) signaling pathways regulate fibrosis: the canonical TGF-β signaling pathway, represented by SMAD-2 and SMAD-3, and the noncanonical pathway, which functions without SMAD-2/3 participation and currently includes TGF-β/mitogen-activated protein kinases, TGF-β/SMAD-1/5, TGF-β/phosphatidylinositol-3-kinase/Akt, TGF-β/Janus kinase/signal transducer and activator of transcription protein-3, and TGF-β/rho-associated coiled-coil containing kinase signaling pathways. MicroRNA (miRNA), a type of non-coding single-stranded small RNA, comprises approximately 22 nucleotides encoded by endogenous genes, which can regulate physiological and pathological processes in fibrotic diseases, particularly affecting organs such as the liver, the kidney, the lungs, and the heart. The aim of this review is to introduce the characteristics of the canonical and non-canonical TGF-β signaling pathways and to classify miRNAs with regulatory effects on these two pathways based on the influenced organ. Further, we aim to summarize the limitations of the current research of the mechanisms of fibrosis, provide insights into possible future research directions, and propose therapeutic options for fibrosis.

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