Molecular mechanisms of inflammasome signaling DOI Open Access
Anukriti Mathur, Jenni A. Hayward, Si Ming Man

et al.

Journal of Leukocyte Biology, Journal Year: 2017, Volume and Issue: 103(2), P. 233 - 257

Published: Aug. 31, 2017

The inflammasome is a macromolecular protein complex that mediates proteolytic cleavage of pro-IL-1β and -IL-18 induces cell death in the form pyroptosis. Certain nucleotide-binding oligomerization domain-like receptors (NLRs), absent melanoma 2 (AIM2)-like (ALRs), or tripartite motif (TRIM) family trigger assembly an response to pathogen-associated molecular patterns (PAMPs) danger-associated (DAMPs). Recent studies have revealed multitude host components signals are essential for controlling canonical noncanonical activation These include pore-forming gasdermin proteins, never mitosis A-related kinase 7 (NEK7), IFN-inducible proteins (IFIs), reactive oxygen species (ROS), autophagy, potassium efflux, mitochondrial perturbations, microbial metabolites. Here, we provide comprehensive overview signaling mechanisms stringent regulation over effector functions inflammasome.

Language: Английский

Obesity, Leptin and Breast Cancer: Epidemiological Evidence and Proposed Mechanisms DOI Open Access
Sebastiano Andò, Luca Gelsomino,

Salvatore Panza

et al.

Cancers, Journal Year: 2019, Volume and Issue: 11(1), P. 62 - 62

Published: Jan. 9, 2019

The prevalence of obesity has been steadily increasing over the past few decades in several developed and developing countries, with resultant hazardous health implications. Substantial epidemiological evidence shown that excessive adiposity strongly influences risk, prognosis, progression various malignancies, including breast cancer. Indeed, it is now well recognized a complex physiologic state associated multiple molecular changes capable modulating behavior tumor cells as surrounding microenvironment. Particularly, insulin resistance, hyperactivation insulin-like growth factor pathways, increased levels estrogen due to aromatization by adipose tissue, inflammatory cytokines, adipokines contribute cancerogenesis. Among adipokines, leptin, whose circulating increase proportionally total tissue mass, identified key member network obesity. This review summarizes current knowledge on link existing between cancer outlines mechanisms underlying this connection. multifaceted role adipokine leptin respect also discussed.

Language: Английский

Citations

183
Obesity promotes resistance to anti-VEGF therapy in breast cancer by up-regulating IL-6 and potentially FGF-2 DOI Open Access
João Incio, Jennifer A. Ligibel, Daniel T. McManus

et al.

Science Translational Medicine, Journal Year: 2018, Volume and Issue: 10(432)

Published: March 14, 2018

Anti-vascular endothelial growth factor (VEGF) therapy has failed to improve survival in patients with breast cancer (BC). Potential mechanisms of resistance anti-VEGF include the up-regulation alternative angiogenic and proinflammatory factors. Obesity is associated hypoxic adipose tissues, including those breast, resulting increased production some aforementioned Hence, we hypothesized that obesity could contribute therapy's lack efficacy. We found BC harbored systemic concentrations interleukin-6 (IL-6) and/or fibroblast 2 (FGF-2), their tumor vasculature was less sensitive treatment. Mouse models revealed impairs effects on angiogenesis, growth, metastasis. In one murine model, IL-6 from adipocytes myeloid cells within tumors. blockade abrogated obesity-induced primary metastatic sites by directly affecting cell proliferation, normalizing vasculature, alleviating hypoxia, reducing immunosuppression. Similarly, a second mouse where FGF-2, normalization FGF-2 expression metformin or specific FGF receptor inhibition decreased vessel density restored sensitivity obese mice. Collectively, our data indicate fuels via inflammatory

Language: Английский

Citations

182
Inflammation-Induced Tumorigenesis and Metastasis DOI Open Access
Sana Hibino, Tetsuro Kawazoe, Hidenori Kasahara

et al.

International Journal of Molecular Sciences, Journal Year: 2021, Volume and Issue: 22(11), P. 5421 - 5421

Published: May 21, 2021

Inflammation, especially chronic inflammation, plays a pivotal role in tumorigenesis and metastasis through various mechanisms is now recognized as hallmark of cancer an attractive therapeutic target cancer. In this review, we discuss recent advances molecular how inflammation promotes suppresses anti-tumor immunity types solid tumors, including esophageal, gastric, colorectal, liver, pancreatic well hematopoietic malignancies.

Language: Английский

Citations

176
Obesity, Type 2 Diabetes, and Cancer Risk DOI Creative Commons

Tiffany Scully,

Abora Ettela,

Derek LeRoith

et al.

Frontiers in Oncology, Journal Year: 2021, Volume and Issue: 10

Published: Feb. 2, 2021

Obesity and type 2 diabetes have both been associated with increased cancer risk are becoming increasingly prevalent. Metabolic abnormalities such as insulin resistance dyslipidemia obesity implicated in the obesity-cancer relationship. Multiple mechanisms proposed to link progression, including an increase insulin/IGF-1 signaling, lipid glucose uptake metabolism, alterations profile of cytokines, chemokines, adipokines, well changes adipose tissue directly adjacent sites. This review aims summarize provide update on epidemiological mechanistic evidence linking cancer, focusing roles insulin, lipids, tissue.

Language: Английский

Citations

166
Obesity and aging: Molecular mechanisms and therapeutic approaches DOI
Ana L. Santos,

Sanchari Sinha

Ageing Research Reviews, Journal Year: 2021, Volume and Issue: 67, P. 101268 - 101268

Published: Feb. 6, 2021

Language: Английский

Citations

160
Cell-Type-Specific Responses to Interleukin-1 Control Microbial Invasion and Tumor-Elicited Inflammation in Colorectal Cancer DOI Creative Commons

Oxana Dmitrieva-Posocco,

Amiran Dzutsev,

David Posocco

et al.

Immunity, Journal Year: 2019, Volume and Issue: 50(1), P. 166 - 180.e7

Published: Jan. 1, 2019

Language: Английский

Citations

156
Lower Airway Dysbiosis Affects Lung Cancer Progression DOI Open Access
Jun-Chieh J. Tsay, Benjamin G. Wu, Imran Sulaiman

et al.

Cancer Discovery, Journal Year: 2020, Volume and Issue: 11(2), P. 293 - 307

Published: Nov. 11, 2020

In lung cancer, enrichment of the lower airway microbiota with oral commensals commonly occurs, and

Language: Английский

Citations

147
NLRP3 inflammasome-mediated cytokine production and pyroptosis cell death in breast cancer DOI Creative Commons
Sara Socorro Faria, Susan Costantini, Vladmir Cláudio Cordeiro de Lima

et al.

Journal of Biomedical Science, Journal Year: 2021, Volume and Issue: 28(1)

Published: April 12, 2021

Breast cancer is the most diagnosed malignancy in women. Increasing evidence has highlighted importance of chronic inflammation at local and/or systemic level breast pathobiology, influencing its progression, metastatic potential and therapeutic outcome by altering tumor immune microenvironment. These processes are mediated a variety cytokines, chemokines growth factors that exert their biological functions either locally or distantly. Inflammasomes protein signaling complexes form response to damage- pathogen-associated molecular patterns (DAMPS PAMPS), triggering release pro-inflammatory cytokines. The dysregulation inflammasome activation can lead development inflammatory diseases, neurodegeneration, cancer. A crucial pathway leading acute occurs through NLRP3 followed caspase 1-dependent IL-1β IL-18 as well as, gasdermin D-mediated pyroptotic cell death. In this review we focus on role components signaling, highlighting more detailed understanding clinical relevance these pathways could significantly contribute novel strategies for

Language: Английский

Citations

127
Context-dependent functions of pattern recognition receptors in cancer DOI
Si Ming Man, Brendan J. Jenkins

Nature reviews. Cancer, Journal Year: 2022, Volume and Issue: 22(7), P. 397 - 413

Published: March 30, 2022

Language: Английский

Citations

86
Harnessing innate immune pathways for therapeutic advancement in cancer DOI Creative Commons

An-Kang Hu,

Li Sun,

Hao Lin

et al.

Signal Transduction and Targeted Therapy, Journal Year: 2024, Volume and Issue: 9(1)

Published: March 25, 2024

Abstract The innate immune pathway is receiving increasing attention in cancer therapy. This ubiquitous across various cell types, not only cells but also adaptive cells, tumor and stromal cells. Agonists targeting the have shown profound changes microenvironment (TME) improved prognosis preclinical studies. However, to date, clinical success of drugs remains limited. Interestingly, recent studies that activation can paradoxically promote progression. uncertainty surrounding therapeutic effectiveness targeted for a critical issue needs immediate investigation. In this review, we observe role demonstrates heterogeneity, linked development stage, status, specific types. We propose within TME, exhibits multidimensional diversity. diversity fundamentally rooted cellular heterogeneity manifested as variety signaling networks. pro-tumor effect essentially reflects suppression classical pathways potential alternative pathways. Refining our understanding tumor’s network employing appropriate strategies enhance ability harness anti-tumor ultimately bridge gap from application.

Language: Английский

Citations

56