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

Remodeling the Tumor Microenvironment with Emerging Nanotherapeutics DOI
Qin Chen,

Guangxuan Liu,

Shuo Liu

et al.

Trends in Pharmacological Sciences, Journal Year: 2017, Volume and Issue: 39(1), P. 59 - 74

Published: Nov. 15, 2017

Language: Английский

Citations

211
Identification of EMT signaling cross-talk and gene regulatory networks by single-cell RNA sequencing DOI Creative Commons
Abhijeet Deshmukh, Suhas Vasaikar, Katarzyna Tomczak

et al.

Proceedings of the National Academy of Sciences, Journal Year: 2021, Volume and Issue: 118(19)

Published: May 3, 2021

The epithelial-to-mesenchymal transition (EMT) plays a critical role during normal development and in cancer progression. EMT is induced by various signaling pathways, including TGF-β, BMP, Wnt-β-catenin, NOTCH, Shh, receptor tyrosine kinases. In this study, we performed single-cell RNA sequencing on MCF10A cells undergoing TGF-β1 stimulation. Our comprehensive analysis revealed that progress through at different paces. Using pseudotime clustering reconstruction of gene-expression profiles EMT, found sequential parallel activation pathways. We also observed transitional cellular states EMT. identified regulatory nodes drive with the expression important microRNAs transcription factors. random circuit perturbation methodology, demonstrate NOTCH pathway acts as key driver TGF-β-induced Furthermore, gene signatures clusters corresponding to intermediate hybrid state are associated poor patient outcome. Overall, study provides insight into context-specific drivers progression highlights complexities process.

Language: Английский

Citations

211
A Systematic Review of miR-29 in Cancer DOI Creative Commons
Jason J. Kwon,

Tricia D. Factora,

Shatovisha Dey

et al.

Molecular Therapy — Oncolytics, Journal Year: 2018, Volume and Issue: 12, P. 173 - 194

Published: Dec. 31, 2018

MicroRNAs (miRNA) are small non-coding RNAs (∼22 nt in length) that known as potent master regulators of eukaryotic gene expression. miRNAs have been shown to play a critical role cancer pathogenesis, and the misregulation is well-known feature cancer. In recent years, miR-29 has emerged miRNA various cancers, it regulate multiple oncogenic processes, including epigenetics, proteostasis, metabolism, proliferation, apoptosis, metastasis, fibrosis, angiogenesis, immunomodulation. Although thoroughly documented tumor suppressor majority studies, some controversy remains with conflicting reports an oncogene. this review, we provide systematic overview miR-29's functional mechanisms introspection on contradictory roles miR-29.

Language: Английский

Citations

204
Hydro-Seq enables contamination-free high-throughput single-cell RNA-sequencing for circulating tumor cells DOI Creative Commons

Yu-Heng Cheng,

Yu‐Chih Chen, Eric Lin

et al.

Nature Communications, Journal Year: 2019, Volume and Issue: 10(1)

Published: May 15, 2019

Abstract Molecular analysis of circulating tumor cells (CTCs) at single-cell resolution offers great promise for cancer diagnostics and therapeutics from simple liquid biopsy. Recent development massively parallel RNA-sequencing (scRNA-seq) provides a powerful method to resolve the cellular heterogeneity gene expression pathway regulation analysis. However, scarcity CTCs massive contamination blood limit utility currently available technologies. Here, we present Hydro-Seq, scalable hydrodynamic scRNA-seq barcoding technique, high-throughput CTC High cell-capture efficiency removal capability Hydro-Seq enables successful 666 21 breast patient samples high throughput. We identify drug targets hormone targeted therapies tracked individual that express markers stem (CSCs) as well epithelial/mesenchymal cell state transitions. Transcriptome these insights into monitoring target processes underlying metastasis.

Language: Английский

Citations

202
The complexity of TRIM28 contribution to cancer DOI Creative Commons
Patrycja Czerwińska,

Sylwia Mazurek,

Maciej Wiznerowicz

et al.

Journal of Biomedical Science, Journal Year: 2017, Volume and Issue: 24(1)

Published: Aug. 29, 2017

Since the first discovery in 1996, engagement of TRIM28 distinct aspects cellular biology has been extensively studied resulting identification a complex nature protein. In this review, we summarize core biological functions that emerge from multi-domain structure and possessed enzymatic activities. Moreover, will discuss whether complexity cancer makes possible candidate for targeted anti-cancer therapy. Briefly, demonstrate role regulation target gene transcription, response to DNA damage, downregulation p53 activity, stimulation epithelial-to-mesenchymal transition, stemness sustainability, induction autophagy retrotransposition, provide answer as stimulator or inhibitor tumorigenesis. To date, number studies significant upregulation expression tissues which correlates with worse overall patient survival, suggesting supports progression. Here, present involvement cell homeostasis collectively imply pro-tumorigenic character TRIM28. Thorough analyses are further needed verify possess potential become new target.

Language: Английский

Citations

195
TGF-β-Induced Endothelial to Mesenchymal Transition in Disease and Tissue Engineering DOI Creative Commons
Jin Ma, Gonzalo Sánchez‐Duffhues, Marie‐José Goumans

et al.

Frontiers in Cell and Developmental Biology, Journal Year: 2020, Volume and Issue: 8

Published: April 21, 2020

Endothelial to mesenchymal transition (EndMT) is a complex biological process that gives rise cells with multipotent potential. EndMT essential for the formation of cardiovascular system during embryonic development. Emerging results link postnatal onset and progression fibrotic diseases cancer. Moreover, recent reports have emphasized potential in tissue engineering regenerative applications by regulating differentiation status cells. Transforming growth factor β (TGF-β) engages many important physiological processes potent inducer EndMT. In this review, we first summarize mechanisms TGF-β signaling pathway as it relates Thereafter, discuss pivotal role TGF-β-induced development diseases, fibrosis cancer, well application engineering.

Language: Английский

Citations

190
The lncRNA GATA6-AS epigenetically regulates endothelial gene expression via interaction with LOXL2 DOI Creative Commons
Philipp Neumann, Nicolas Jaé,

Andrea Knau

et al.

Nature Communications, Journal Year: 2018, Volume and Issue: 9(1)

Published: Jan. 10, 2018

Impaired or excessive growth of endothelial cells contributes to several diseases. However, the functional involvement regulatory long non-coding RNAs in these processes is not well defined. Here, we show that antisense transcript GATA6 (GATA6-AS) interacts with epigenetic regulator LOXL2 regulate gene expression via changes histone methylation. Using RNA deep sequencing, find GATA6-AS upregulated during hypoxia. Silencing diminishes TGF-β2-induced endothelial-mesenchymal transition vitro and promotes formation blood vessels mice. We identify LOXL2, known remove activating H3K4me3 chromatin marks, as a GATA6-AS-associated protein, reveal set angiogenesis-related genes are inversely regulated by silencing. As silencing reduces methylation two genes, periostin cyclooxygenase-2, conclude acts negative nuclear function.

Language: Английский

Citations

182
Chemoresistance and the Self-Maintaining Tumor Microenvironment DOI Open Access

Gulcen Yeldag,

Alistair Rice, Armando E. del Río Hernández

et al.

Cancers, Journal Year: 2018, Volume and Issue: 10(12), P. 471 - 471

Published: Nov. 28, 2018

The progression of cancer is associated with alterations in the tumor microenvironment, including changes extracellular matrix (ECM) composition, rigidity, hypervascularization, hypoxia, and paracrine factors. One key malignant phenotype cells their ability to resist chemotherapeutics, elements ECM can promote chemoresistance through a variety signaling pathways, inducing gene expression protein activity that allow resistance. Furthermore, maintained as an environment facilitates chemoresistance, since its constitution modulates cancer-associated cells, which themselves affect microenvironment. In this review, we discuss how properties microenvironment interplay between these external stimuli. We focus on both response environment, well maintenance chemoresistant emerges from complex network present.

Language: Английский

Citations

180
The paradox of Th17 cell functions in tumor immunity DOI
Zahra Asadzadeh, Hamed Mohammadi, Elham Safarzadeh

et al.

Cellular Immunology, Journal Year: 2017, Volume and Issue: 322, P. 15 - 25

Published: Oct. 31, 2017

Language: Английский

Citations

178
The FUS/circEZH2/KLF5/ feedback loop contributes to CXCR4-induced liver metastasis of breast cancer by enhancing epithelial-mesenchymal transition DOI Creative Commons
Peng Liu, Zehao Wang,

Xueqi Ou

et al.

Molecular Cancer, Journal Year: 2022, Volume and Issue: 21(1)

Published: Oct. 12, 2022

Abstract Background Metastasis of breast cancer have caused the majority cancer-related death worldwide. The circRNAs are associated with tumorigenesis and metastasis in according to recent research. However, biological mechanism liver metastatic remains ambiguous yet. Methods Microarray analysis three pairs primary BC tissues matched hepatic specimens identified circEZH2. We used RT-qPCR FISH assays confirm circEZH2 existence, characteristics, expression. Both vivo vitro, played an oncogenic role which promoted as well. A range bioinformatic analysis, Western blot, RNA pull-down, RIP, ChIP, animal experiments were define feedback loop involving FUS, circEZH2, miR-217-5p, KLF5, CXCR4 well epithelial mesenchymal transition. Results In our research, was proved be upregulated metastases predicted worse prognosis patients. Overexpression notably accentuated vitality invasion cells, whereas knockdown elicited literally opposite effects. Besides, overexpressed vivo. Moreover, could adsorb miR-217-5p upregulate KLF5 thus leading activate FUS transcription would facilitate back-splicing program Meanwhile, transcriptionally accelerate transition cancer. Conclusions Consequently, a novel FUS/circEZH2/KLF5/CXCR4 established while biomarker potential target for patients’ therapy.

Language: Английский

Citations

133