Single cell analysis in head and neck cancer reveals potential immune evasion mechanisms during early metastasis DOI Creative Commons
Hong Sheng Quah, Elaine Yiqun Cao, Lisda Suteja

et al.

Nature Communications, Journal Year: 2023, Volume and Issue: 14(1)

Published: March 27, 2023

Profiling tumors at single-cell resolution provides an opportunity to understand complexities underpinning lymph-node metastases in head and neck squamous-cell carcinoma. Single-cell RNAseq (scRNAseq) analysis of cancer-cell trajectories identifies a subpopulation pre-metastatic cells, driven by actionable pathways including AXL AURK. Blocking these two proteins blunts tumor invasion patient-derived cultures. Furthermore, scRNAseq analyses tumor-infiltrating CD8 + T-lymphocytes show distinct T-cell dysfunction, corroborated their clonal architecture based on receptor sequencing. By determining key modulators trajectories, followed validation using external datasets functional experiments, we uncover role for SOX4 mediating exhaustion. Finally, interactome between cells putative the Midkine pathway immune-modulation this is confirmed from humanized mice. Aside specific findings, study demonstrates importance heterogeneity identifying vulnerabilities during early metastasis.

Language: Английский

EMT in cancer DOI
Thomas Brabletz, Raghu Kalluri, M. Ángela Nieto

et al.

Nature reviews. Cancer, Journal Year: 2018, Volume and Issue: 18(2), P. 128 - 134

Published: Jan. 12, 2018

Language: Английский

Citations

1658
Natural Killer Cells: Development, Maturation, and Clinical Utilization DOI Creative Commons

Alex M. Abel,

Chao Yang, Monica S. Thakar

et al.

Frontiers in Immunology, Journal Year: 2018, Volume and Issue: 9

Published: Aug. 13, 2018

Natural killer cells are the predominant innate lymphocyte subsets that mediate anti-tumor and anti-viral responses, therefore possess promising clinical utilization. NK do not express polymorphic clonotypic receptors utilize inhibitory (KIR Ly49) to develop, mature, recognize 'self' from 'non-self'. The essential roles of common gamma cytokines such as IL-2, IL-7, IL-15 in commitment development well-established. However, critical functions proinflammatory IL-12, IL-18, IL-27, IL-35 transcriptional-priming only starting emerge. Recent studies have highlighted multiple shared characteristics between adaptive immune lymphocytes. unique signaling pathways offer exclusive ways genetically manipulate improve their effector functions. Here, we summarize recent advances made understanding how potential translational use clinic.

Language: Английский

Citations

944
Diverging inflammasome signals in tumorigenesis and potential targeting DOI
Rajendra Karki, Thirumala‐Devi Kanneganti

Nature reviews. Cancer, Journal Year: 2019, Volume and Issue: 19(4), P. 197 - 214

Published: March 6, 2019

Language: Английский

Citations

537
Role of EMT in Metastasis and Therapy Resistance DOI Open Access

Bethany Smith,

Neil A. Bhowmick

Journal of Clinical Medicine, Journal Year: 2016, Volume and Issue: 5(2), P. 17 - 17

Published: Jan. 27, 2016

Epithelial–mesenchymal transition (EMT) is a complex molecular program that regulates changes in cell morphology and function during embryogenesis tissue development. EMT also contributes to tumor progression metastasis. Cells undergoing expand out of degrade the surrounding microenvironment subsequently migrate from primary site. The mesenchymal phenotype observed fibroblasts specifically important based on expression smooth muscle actin (α-SMA), fibroblast growth factor (FGF), fibroblast-specific protein-1 (FSP1), collagen enhance EMT. Although not completely dependent regulators such as Snail, Twist, Zeb-1/-2, analysis upstream signaling (i.e., TGF-β, EGF, Wnt) necessary understand more comprehensively. Tumor epithelial–fibroblast interactions regulate have been identified prostate cancer. cellular crosstalk significant because these events influence therapy response patient outcome. This review addresses how canonical signals originating cancer contribute metastasis recurrence after therapy.

Language: Английский

Citations

444
EMT: Mechanisms and therapeutic implications DOI
Mohini Singh,

Nicolas Yelle,

Chitra Venugopal

et al.

Pharmacology & Therapeutics, Journal Year: 2017, Volume and Issue: 182, P. 80 - 94

Published: Aug. 20, 2017

Language: Английский

Citations

404
Melatonin, a Full Service Anti-Cancer Agent: Inhibition of Initiation, Progression and Metastasis DOI Open Access
Russel J. Reıter, Sergio Rosales‐Corral,

Dun‐Xian Tan

et al.

International Journal of Molecular Sciences, Journal Year: 2017, Volume and Issue: 18(4), P. 843 - 843

Published: April 17, 2017

There is highly credible evidence that melatonin mitigates cancer at the initiation, progression and metastasis phases. In many cases, molecular mechanisms underpinning these inhibitory actions have been proposed. What rather perplexing, however, large number of processes by which reportedly restrains development growth. These diverse suggest what being observed are merely epiphenomena an underlying more fundamental action remains to be disclosed. Some arresting on clearly membrane receptor-mediated while others receptor-independent involve direct intracellular this ubiquitously-distributed molecule. While emphasis melatonin/cancer research has role indoleamine in restraining breast cancer, changing quickly with types having shown susceptible inhibition melatonin. several facets could immediate applications clinical level. Many studies melatonin's co-administration improves sensitivity cancers conventional drugs. Even important findings renders previously totally resistant treatment sensitive same therapies. Melatonin also inhibits associated limiting entrance cells into vascular system preventing them from establishing secondary growths distant sites. This particular importance since often significantly contributes death patient. Another area deserves additional consideration related capacity reducing toxic consequences anti-cancer drugs increasing their efficacy. Although information available for than a decade, it not adequately exploited if only beneficial patients its ability attenuate acute long-term drug toxicity, should used improve physical wellbeing patients. The experimental findings, advantages using as co-treatment therapies would far exceed improvements

Language: Английский

Citations

391
Epigenetics in cancer stem cells DOI Creative Commons
Tan Boon Toh, Jhin Jieh Lim, Edward Kai‐Hua Chow

et al.

Molecular Cancer, Journal Year: 2017, Volume and Issue: 16(1)

Published: Feb. 1, 2017

Compelling evidence have demonstrated that bulk tumors can arise from a unique subset of cells commonly termed "cancer stem cells" has been proposed to be strong driving force tumorigenesis and key mechanism therapeutic resistance. Recent advances in epigenomics illuminated mechanisms by which epigenetic regulation contribute cancer progression. In this review, we present discussion how deregulation various pathways initiation tumorigenesis, particularly with respect maintenance survival cells. This information, together several promising clinical preclinical trials modulating drugs, offer new possibilities for targeting as well improving therapy overall.

Language: Английский

Citations

369
Cancer metastasis: Mechanisms of inhibition by melatonin DOI Open Access
Shih‐Chi Su, Ming‐Ju Hsieh,

Wei‐En Yang

et al.

Journal of Pineal Research, Journal Year: 2016, Volume and Issue: 62(1)

Published: Oct. 12, 2016

Abstract Melatonin is a naturally occurring molecule secreted by the pineal gland and known as gatekeeper of circadian clocks. Mounting evidence indicates that melatonin, employing multiple interrelated mechanisms, exhibits variety oncostatic properties in myriad tumors during different stages their progression. Tumor metastasis, which commonly occurs at late stage, responsible for majority cancer deaths; metastases lead to development secondary distant from primary site. In reference vast investigations have focused on tumor progression Recently, however, interest has shifted toward role melatonin metastases. this review, we highlight current advances understanding molecular mechanisms counteracts metastases, including experimental clinical observations; emphasis placed impact both non‐neoplastic cells within microenvironment. Due broad range melatonin's actions, underlying its ability interfere with are numerous. These include modulation cell–cell cell–matrix interaction, extracellular matrix remodeling metalloproteinases, cytoskeleton reorganization, epithelial–mesenchymal transition, angiogenesis. The discussed herein will serve solid foundation urging basic studies use understand control metastatic diseases.

Language: Английский

Citations

267
The basics of epithelial–mesenchymal transition (EMT): A study from a structure, dynamics, and functional perspective DOI

Vishal Das,

Sourya Bhattacharya, Channakeshavaiah Chikkaputtaiah

et al.

Journal of Cellular Physiology, Journal Year: 2019, Volume and Issue: 234(9), P. 14535 - 14555

Published: Feb. 5, 2019

Abstract Epithelial–mesenchymal transition (EMT) is a key step in transdifferentiation process solid cancer development. Forthcoming evidence suggest that the stratified program transforms polarized, immotile epithelial cells to migratory mesenchymal associated with enhancement of breast stemness, metastasis, and drug resistance. It involves primarily several signaling pathways, such as transforming growth factor‐β (TGF‐β), cadherin, notch, plasminogen activator protein inhibitor, urokinase activator, WNT/beta catenin pathways. However, current understanding on crosstalk multisignaling pathways assemblies transcription factors remain be explored. In this review, we focus signal transduction linked therapeutic development strategies. We have also performed computational modeling indepth structure conformational dynamic studies regulatory proteins analyze molecular interactions their associate understand complicated EMT progression metastasis. Electrostatic potential surfaces been analyzed help optimization electrostatic between its ligand. Therefore, biological implications underlying through biology biocomputation structural approaches will enable new strategies sensitize tumors conventional therapy suppress metastatic phenotype.

Language: Английский

Citations

227
Breast Cancer Metastasis: Mechanisms and Therapeutic Implications DOI Open Access

Misung Park,

Do‐Hee Kim,

Sunghyub Ko

et al.

International Journal of Molecular Sciences, Journal Year: 2022, Volume and Issue: 23(12), P. 6806 - 6806

Published: June 18, 2022

Breast cancer is the most common malignancy in women worldwide. Metastasis leading cause of high mortality cancers. Although predicting early stage breast before metastasis can increase survival rate, often discovered or diagnosed after has occurred. In general, a poor prognosis because it starts as local disease and spread to lymph nodes distant organs, contributing significant impediment treatment. Metastatic cells acquire aggressive characteristics from tumor microenvironment (TME) through several mechanisms including epithelial–mesenchymal transition (EMT) epigenetic regulation. Therefore, understanding nature mechanism facilitate development targeted therapeutics focused on metastasis. This review discusses current therapies improve diagnosis patients with metastatic cancer.

Language: Английский

Citations

212