scholarly journals Role of IQGAP1 in Carcinogenesis

Cancers ◽  
2021 ◽  
Vol 13 (16) ◽  
pp. 3940
Author(s):  
Tao Wei ◽  
Paul F. Lambert
Keyword(s):  
Immune Responses ◽  
Signaling Pathways ◽  
Critical Role ◽  
Molecular Evidence ◽  
Scaffolding Proteins ◽  
Review Of The Literature ◽  
Gtpase Activating Protein ◽  
Iq Motif ◽  
Different Types

Scaffolding proteins can play important roles in cell signaling transduction. IQ motif-containing GTPase-activating protein 1 (IQGAP1) influences many cellular activities by scaffolding multiple key signaling pathways, including ones involved in carcinogenesis. Two decades of studies provide evidence that IQGAP1 plays an essential role in promoting cancer development. IQGAP1 is overexpressed in many types of cancer, and its overexpression in cancer is associated with lower survival of the cancer patient. Here, we provide a comprehensive review of the literature regarding the oncogenic roles of IQGAP1. We start by describing the major cancer-related signaling pathways scaffolded by IQGAP1 and their associated cellular activities. We then describe clinical and molecular evidence for the contribution of IQGAP1 in different types of cancers. In the end, we review recent evidence implicating IQGAP1 in tumor-related immune responses. Given the critical role of IQGAP1 in carcinoma development, anti-tumor therapies targeting IQGAP1 or its associated signaling pathways could be beneficial for patients with many types of cancer.

Classic and Novel Signaling Pathways Involved in Cancer: Targeting the NF-κB and Syk Signaling Pathways

2019 ◽  
Vol 14 (3) ◽  
pp. 219-225 ◽  
Author(s):  
Cong Tang ◽  
Guodong Zhu
Keyword(s):  
Cancer Therapy ◽  
Tyrosine Kinase ◽  
Signaling Pathways ◽  
Molecular Mechanisms ◽  
Therapeutic Potential ◽  
Cell Receptor ◽  
Transmembrane Receptors ◽  
Biological Responses ◽  
Different Types

The nuclear factor kappa B (NF-κB) consists of a family of transcription factors involved in the regulation of a wide variety of biological responses. Growing evidence support that NF-κB plays a major role in oncogenesis as well as its well-known function in the regulation of immune responses and inflammation. Therefore, we made a review of the diverse molecular mechanisms by which the NF-κB pathway is constitutively activated in different types of human cancers and the potential role of various oncogenic genes regulated by this transcription factor in cancer development and progression. We also discussed various pharmacological approaches employed to target the deregulated NF-κB signaling pathway and their possible therapeutic potential in cancer therapy. Moreover, Syk (Spleen tyrosine kinase), non-receptor tyrosine kinase which mediates signal transduction downstream of a variety of transmembrane receptors including classical immune-receptors like the B-cell receptor (BCR), which can also activate the inflammasome and NF-κB-mediated transcription of chemokines and cytokines in the presence of pathogens would be discussed as well. The highlight of this review article is to summarize the classic and novel signaling pathways involved in NF-κB and Syk signaling and then raise some possibilities for cancer therapy.

scholarly journals Interplay Between SOX9, Wnt/β-Catenin and Androgen Receptor Signaling in Castration-Resistant Prostate Cancer

2019 ◽  
Vol 20 (9) ◽  
pp. 2066 ◽  
Author(s):  
Namrata Khurana ◽  
Suresh C. Sikka
Keyword(s):  
Prostate Cancer ◽  
Androgen Receptor ◽  
Signaling Pathways ◽  
Critical Role ◽  
Castration Resistant Prostate Cancer ◽  
Form Complex ◽  
Androgen Receptor Signaling ◽  
Castration Resistant ◽  
Signaling Axis

Androgen receptor (AR) signaling plays a key role not only in the initiation of prostate cancer (PCa) but also in its transition to aggressive and invasive castration-resistant prostate cancer (CRPC). However, the crosstalk of AR with other signaling pathways contributes significantly to the emergence and growth of CRPC. Wnt/β-catenin signaling facilitates ductal morphogenesis in fetal prostate and its anomalous expression has been linked with PCa. β-catenin has also been reported to form complex with AR and thus augment AR signaling in PCa. The transcription factor SOX9 has been shown to be the driving force of aggressive and invasive PCa cells and regulate AR expression in PCa cells. Furthermore, SOX9 has also been shown to propel PCa by the reactivation of Wnt/β-catenin signaling. In this review, we discuss the critical role of SOX9/AR/Wnt/β-catenin signaling axis in the development and progression of CRPC. The phytochemicals like sulforaphane and curcumin that can concurrently target SOX9, AR and Wnt/β-catenin signaling pathways in PCa may thus be beneficial in the chemoprevention of PCa.

scholarly journals Critical role of the IgM Fc receptor in IgM homeostasis, B-cell survival, and humoral immune responses

2012 ◽  
Vol 109 (40) ◽  
pp. E2699-E2706 ◽  
Author(s):  
R. Ouchida ◽  
H. Mori ◽  
K. Hase ◽  
H. Takatsu ◽  
T. Kurosaki ◽  
...  
Keyword(s):  
Immune Responses ◽  
B Cell ◽  
Cell Survival ◽  
Critical Role ◽  
Fc Receptor ◽  
Humoral Immune ◽  
Humoral Immune Responses ◽  
B Cell Survival

Abstract 636: Gut Microflora Influences Pathology in the Kawasaki Disease (KD) Vasculitis Mouse Model

2015 ◽  
Vol 35 (suppl_1) ◽  
Author(s):  
Daiko Wakita ◽  
Yosuke Kurashima ◽  
Yoshihiro Takasato ◽  
Youngho Lee ◽  
Kenichi Shimada ◽  
...  
Keyword(s):  
Mouse Model ◽  
Immune Responses ◽  
Critical Role ◽  
Gut Microflora ◽  
Vascular Abnormalities ◽  
Coronary Arteritis ◽  
Specific Pathogen ◽  
New Perspective ◽  
Bacteria And Fungi

Background: KD is the leading cause of acquired heart disease in the US. We have demonstrated the critical role of innate immune responses via IL-1R/MyD88 signaling in the Lactobacillus casei cell wall extract (LCWE)-induced KD mouse model. The diversity and composition of microflora (both bacterial and fungal) have been associated with the regulation and alterations of immune responses and various pathologies. However, the role of gut microbiota in immunopathology of KD has not been investigated. Objective: To evaluate the role of gut microflora in development of coronary arteritis, and vascular abnormalities in KD mouse model. Methods and Results: We investigated the role of gut microflora in the LCWE-induced KD mouse model, using Specific-Pathogen Free (SPF) and Germ Free (GF) mice (C57BL/6). GF mice showed a significant decrease of KD lesions, including coronary arteritis compared with SPF mice. The development of LCWE-induced AAA, which we recently discovered in this mouse model, was also markedly diminished in GF mice. In addition to GF mice, we also investigated the specific role of commensal bacteria and/or fungi, and determined whether altered microorganism burden in this KD mouse model contributes to disease severity. To deplete bacteria and/or fungi in the gut microflora, we exposed pregnant SPF mice and their offspring to antibiotics cocktail (Abx) or antifungal drug (fluconazole; Fluc) in their drinking water for 5 wks and induced KD. The mice treated with Abx or Fluc had significantly reduced coronary arteritis and AAA compared to controls. The Abx plus Fluc administration showed marked decrease of KD vasculitis. Conclusions: We demonstrate here that gut microflora play a critical role in the development of KD vasculitis in LCWE-induced mouse model. Our results suggest that both bacteria and fungi in the intestinal microbiota may control the induction and severity of KD vasculitis. These findings provide a new perspective on the potential role of the microbiome in KD pathogenesis and may offer new diagnostic and therapeutic strategies for KD patients.

377 - Critical Role of TOB1 in Controlling Intestinal Mucosal Inflammation by Inhibitiing Th1/Th17 Immune Responses in IBD

2018 ◽  
Vol 154 (6) ◽  
pp. S-89
Author(s):  
Caiyun Ma ◽  
Cui Zhang ◽  
Wei Wu ◽  
Mingming Sun ◽  
Zhanju Liu
Keyword(s):  
Immune Responses ◽  
Critical Role ◽  
Mucosal Inflammation

scholarly journals Anti-inflammatory role of curcumin in Lipopolysaccharide treated A549 cells at global proteome level and on mycobacterial infection

2019 ◽  
Author(s):  
Suchita Singh ◽  
Rakesh Arya ◽  
Rhishikesh R Bargaje ◽  
Mrinal Kumar Das ◽  
Subia Akram ◽  
...  
Keyword(s):  
Isotope Labeling ◽  
Small Cell Lung Carcinoma ◽  
Bacterial Load ◽  
Critical Role ◽  
A549 Cells ◽  
Molecular Evidence ◽  
Simultaneous Treatment ◽  
Cell Lung Carcinoma ◽  
Anti Inflammatory

AbstractA diet derived agent Curcumin (Diferuloylmethane), demonstrated its clinical application in inflammation, infection and cancer conditions. Nevertheless, its impact on the proteome of epithelial cells of non-small cell lung carcinoma (NSCLC) is yet to be explored. We employed a stable isotope labeling method for cell culture (SILAC) based relative quantitative proteomics and informatics analysis to comprehend global proteome change in A549 cells treated with curcumin and/or Lipopolysaccharide (LPS). Pretreated A549 cells were infected with Mycobacterium tuberculosis H37Rv strain to monitor bacterial load. With exposure to curcumin and LPS, out of the 1492 identified proteins, 305 and 346 proteins showed deregulation respectively. The expression of BID and AIFM1 mitochondrial proteins which play critical role in apoptotic pathway were deregulated in curcumin treated cells. Higher mitochondria intensity was observed in curcumin treated A549 cells than LPS treatment. Simultaneous treatment of curcumin and LPS neutralized the effect of LPS. Curcumin and/or LPS pretreated A549 cells infected with H37Rv, showed successful bacterial internalization. LPS treated A549 cells after infection showed increased bacterial load than curcumin compared to non-treated infected cells. However, simultaneous treatment of curcumin and LPS neutralized the effect of LPS. This study generated molecular evidence to deepen our understanding of the anti-inflammatory role of curcumin and may be useful to identify molecular targets for drug discovery.

scholarly journals Emerging Role of Exosomes in Tuberculosis: From Immunity Regulations to Vaccine and Immunotherapy

2021 ◽  
Vol 12 ◽  
Author(s):  
Yin-Fu Sun ◽  
Jiang Pi ◽  
Jun-Fa Xu
Keyword(s):  
Immune Responses ◽  
Delivery System ◽  
Immune Modulation ◽  
Immune Cell ◽  
Critical Role ◽  
Cell Communication ◽  
Immune Defense ◽  
Research Progress ◽  
Recent Research Progress

Exosomes are cell-derived nanovesicles carrying protein, lipid, and nucleic acid for secreting cells, and act as significant signal transport vectors for cell-cell communication and immune modulation. Immune-cell-derived exosomes have been found to contain molecules involved in immunological pathways, such as MHCII, cytokines, and pathogenic antigens. Tuberculosis (TB), caused by Mycobacterium tuberculosis (MTB), remains one of the most fatal infectious diseases. The pathogen for tuberculosis escapes the immune defense and continues to replicate despite rigorous and complicate host cell mechanisms. The infected-cell-derived exosomes under this circumstance are found to trigger different immune responses, such as inflammation, antigen presentation, and activate subsequent pathways, highlighting the critical role of exosomes in anti-MTB immune response. Additionally, as a novel kind of delivery system, exosomes show potential in developing new vaccination and treatment of tuberculosis. We here summarize recent research progress regarding exosomes in the immune environment during MTB infection, and further discuss the potential of exosomes as delivery system for novel anti-MTB vaccines and therapies.

scholarly journals The microbiota plays a critical role in the reactivity of lung immune components to innate ligands

2020 ◽  
Author(s):  
Quentin Marquant ◽  
Daphné Laubreton ◽  
Carole Drajac ◽  
Elliot Mathieu ◽  
Edwige Bouguyon ◽  
...  
Keyword(s):  
Immune Responses ◽  
Critical Role ◽  
Innate Immune ◽  
Immune Reactivity ◽  
Innate Immune Responses ◽  
Plain Language ◽  
Pulmonary Tissue ◽  
Germ Free ◽  
Syncytial Virus

AbstractThe microbiota contributes to shaping efficient and safe immune defenses in the gut. However, little is known about the role of the microbiota in the education of pulmonary innate immune responses. Here, we tested whether the endogenous microbiota can modulate reactivity of pulmonary tissue to pathogen stimuli by comparing the response of specific pathogen-free (SPF) and germ-free (GF) mice. Using SPF and GF mice intranasally exposed to lipopolysaccharide (LPS), a component of Gram-negative bacteria, we observed earlier and greater inflammation in the pulmonary compartment of GF mice than that of SPF mice. Toll-like receptor 4 (TLR4) was more abundantly expressed in the lungs of GF mice than those of SPF mice at steady state, which could predispose the innate immunity of GF mice to strongly react to environmental stimuli. Lung explants were stimulated with different TLR agonists or infected with the human airways pathogen, respiratory syncytial virus (RSV), resulting in greater inflammation under almost all conditions for the GF explants. Finally, alveolar macrophages (AM) from GF mice presented a higher innate immune response upon RSV infection than those of SPF mice. Overall, these data suggest that the presence of microbiota in SPF mice induced a process of innate immune tolerance in the lungs by a mechanism which remains to be elucidated. Our study represents a step forward to establishing the link between the microbiota and the immune reactivity of the lungs.Plain Language summaryMicrobiota represents an important partner of immunologic system at the interface between immune cells and epithelium. It is well known, notably in the gut, that the microbiota contributes in shaping efficient and safe defenses. However, little is known about the role of the microbiota in the education of pulmonary innate immune responses. In this study, we postulate that endogenous microbiota could dampen an excessive reactivity of pulmonary tissue to external stimuli. Thus, we sought to study the innate immune reaction switched on by viral or bacterial ligands in respiratory tract cells coming from mice with or without microbiota (germ-free condition, GF). Altogether, our results show a higher inflammatory reaction in GF condition. This study represents a step forward to better establish the link between the microbiota and the reactivity of the lung tissue. Not only these data demonstrate that the microbiota educates the pulmonary innate immune system, but also contributes the emerging concept of using respiratory commensal bacteria as potential next-generation probiotics to prevent susceptibility to respiratory diseases.

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