YTHDF1 promotes breast cancer progression by facilitating FOXM1 translation in an m6A-dependent manner DOI Creative Commons
Hengyu Chen, Yuanhang Yu, Ming Yang

et al.

Cell & Bioscience, Journal Year: 2022, Volume and Issue: 12(1)

Published: Feb. 23, 2022

N6-methyladenosine (m6A) is the most common post-transcriptional modification at RNA level. However, exact molecular mechanisms of m6A epigenetic regulation in breast cancer remain largely unknown and need to be fully elucidated. The integrating bioinformatics analyses were used screen clinical relevance dysregulated "reader" protein YTHDF1 from TCGA databases, which was further validated a cohort specimens. Furthermore, functional experiments such as CCK-8 assay, EdU wound healing transwell invasion assay cell cycle determine biological role cancer. RIP, m6A-IP, CLIP assays find target verification by RT-qPCR, western blot, polysome profiling assay. protein-protein interaction between FOXM1 detected via co-immunoprecipitation.Our study showed that overexpressed cells tissues At same time, high expression level positively correlated with tumor size, lymph node invasion, distant metastasis patients. depletion repressed proliferation, epithelial-mesenchymal transformation (EMT) induced G0/G1 phase arrest vitro vivo. We also demonstrated YTHDF1. Through recognizing binding m6A-modified mRNA FOXM1, accelerated translation process promoted metastasis. Whereas overexpression partially counteracted suppressed effects caused silence, verified regulatory relationship FOXM1.Our reveals novel YTHDF1/FOXM1 pathway contributes progression cancer, suggesting might applied potential biomarker therapeutic target. That advances our understanding tumorigenesis for regulation.

Language: Английский

Oxidative Stress in Cancer DOI Creative Commons
John D. Hayes, Albena T. Dinkova‐Kostova, Kenneth D. Tew

et al.

Cancer Cell, Journal Year: 2020, Volume and Issue: 38(2), P. 167 - 197

Published: July 9, 2020

Language: Английский

Citations

1839
Lactate modulation of immune responses in inflammatory versus tumour microenvironments DOI
Michelangelo Certo, Chin‐Hsien Tsai, Valentina Pucino

et al.

Nature reviews. Immunology, Journal Year: 2020, Volume and Issue: 21(3), P. 151 - 161

Published: Aug. 24, 2020

Language: Английский

Citations

562
The molecular mechanisms and therapeutic strategies of EMT in tumor progression and metastasis DOI Creative Commons

Yuhe Huang,

Weiqi Hong,

Xiawei Wei

et al.

Journal of Hematology & Oncology, Journal Year: 2022, Volume and Issue: 15(1)

Published: Sept. 8, 2022

Abstract Epithelial–mesenchymal transition (EMT) is an essential process in normal embryonic development and tissue regeneration. However, aberrant reactivation of EMT associated with malignant properties tumor cells during cancer progression metastasis, including promoted migration invasiveness, increased stemness, enhanced resistance to chemotherapy immunotherapy. tightly regulated by a complex network which orchestrated several intrinsic extrinsic factors, multiple transcription post-translational control, epigenetic modifications, noncoding RNA-mediated regulation. In this review, we described the molecular mechanisms, signaling pathways, stages tumorigenesis involved discussed dynamic non-binary its role metastasis. Finally, summarized challenges immunotherapy proposed strategies for therapy targeting EMT.

Language: Английский

Citations

492
Linking EMT programmes to normal and neoplastic epithelial stem cells DOI
Arthur W. Lambert, Robert A. Weinberg

Nature reviews. Cancer, Journal Year: 2021, Volume and Issue: 21(5), P. 325 - 338

Published: Feb. 5, 2021

Language: Английский

Citations

404
Long non-coding RNAs towards precision medicine in gastric cancer: early diagnosis, treatment, and drug resistance DOI Creative Commons
Yuan Li, Zhiyuan Xu, Shanming Ruan

et al.

Molecular Cancer, Journal Year: 2020, Volume and Issue: 19(1)

Published: May 27, 2020

Gastric cancer is a deadly disease and remains the third leading cause of cancer-related death worldwide. The 5-year overall survival rate patients with early-stage localized gastric more than 60%, whereas that distant metastasis less 5%. Surgical resection best option for cancer, while chemotherapy mainly used in middle advanced stages this disease, despite frequently reported treatment failure due to resistance. Therefore, there an unmet medical need identifying new biomarkers early diagnosis proper management patients, achieve response treatment. Long non-coding RNAs (lncRNAs) body fluids have attracted widespread attention as screening, diagnosis, treatment, prognosis, responses drugs high specificity sensitivity. In present review, we focus on clinical potential lncRNAs liquid biopsies prognosis cancer. We also comprehensively discuss roles their molecular mechanisms chemoresistance well therapeutic targets precision medicine.

Language: Английский

Citations

265
Hypoxia-Induced Epithelial-Mesenchymal Transition in Cancers: HIF-1α and Beyond DOI Creative Commons
Shing Yau Tam, V. Wu, Hkw Law

et al.

Frontiers in Oncology, Journal Year: 2020, Volume and Issue: 10

Published: April 8, 2020

Metastasis is the main cause of cancer-related mortality. Although actual process metastasis remains largely elusive, epithelial-mesenchymal transition (EMT) has been considered as a major event in metastasis. Besides, hypoxia common solid cancers and an important factor for adverse treatment outcomes including Since EMT potentially share several signaling pathways, many recent studies focused on investigate issue hypoxia-induced EMT. Among all potential mediators EMT, hypoxia-inducible factor-1α (HIF-1α) studied extensively. Moreover, there are other that may also contribute to process. This review aims summarize reports by HIF-1α or provide insights further investigations this issue. Ultimately, better understanding allow us develop anti-metastatic strategies improve outcomes.

Language: Английский

Citations

230
Single-cell transcriptome analysis of tumor and stromal compartments of pancreatic ductal adenocarcinoma primary tumors and metastatic lesions DOI Creative Commons
Wei Lin,

Pawan Noel,

Erkut Borazanci

et al.

Genome Medicine, Journal Year: 2020, Volume and Issue: 12(1)

Published: Sept. 28, 2020

Solid tumors such as pancreatic ductal adenocarcinoma (PDAC) comprise not just tumor cells but also a microenvironment with which the constantly interact. Detailed characterization of cellular composition is critical to understanding disease and treatment patient. Single-cell transcriptomics has been used study different solid types including PDAC. However, almost all those studies primary tissues.In this study, we employed single-cell RNA sequencing technology profile transcriptomes individual from dissociated or metastatic biopsies obtained patients Unsupervised clustering analysis well new supervised classification algorithm, SuperCT, was identify cell within tissues. The expression signatures were then compared between biopsies. expressions type-specific signature genes correlated patient survival using public datasets.Our revealed distinct in PDAC tissues cells, endothelial cancer-associated fibroblasts (CAFs), immune cells. cancer showed high inter-patient heterogeneity, whereas stromal more homogenous across patients. Immune infiltration varies significantly majority being macrophages exhausted lymphocytes. We found that an important factor defining subtypes. Furthermore, levels markers for EMT+ activated CAFs, associated survival.Taken together, our work identifies significant heterogeneity compositions lesions. subtypes outcome. These findings provide valuable insights on could potentially inform management

Language: Английский

Citations

214
Dynamic ROS Control by TIGAR Regulates the Initiation and Progression of Pancreatic Cancer DOI Creative Commons
Eric C. Cheung, Gina M. DeNicola, Colin Nixon

et al.

Cancer Cell, Journal Year: 2020, Volume and Issue: 37(2), P. 168 - 182.e4

Published: Jan. 23, 2020

The TIGAR protein has antioxidant activity that supports intestinal tissue repair and adenoma development. Using a pancreatic ductal adenocarcinoma (PDAC) model, we show reactive oxygen species (ROS) regulation by premalignant tumor initiation while restricting metastasis. Increased ROS in PDAC cells drives phenotypic switch increases migration, invasion, metastatic capacity. This is dependent on increased activation of MAPK signaling can be reverted treatment. In mouse human, expression modulated during development, with higher levels lesions lower metastasizing tumors. Our study indicates temporal, dynamic control underpins full malignant progression helps to rationalize conflicting reports pro- anti-tumor effects

Language: Английский

Citations

199
Emerging role of tumor cell plasticity in modifying therapeutic response DOI Creative Commons
Siyuan Qin, Jingwen Jiang, Yi Lü

et al.

Signal Transduction and Targeted Therapy, Journal Year: 2020, Volume and Issue: 5(1)

Published: Oct. 7, 2020

Abstract Resistance to cancer therapy is a major barrier management. Conventional views have proposed that acquisition of resistance may result from genetic mutations. However, accumulating evidence implicates key role non-mutational mechanisms underlying drug tolerance, the latter which focus will be discussed here. Such processes are largely driven by tumor cell plasticity, renders cells insusceptible drug-targeted pathway, thereby facilitating survival and growth. The concept plasticity highlights significance re-activation developmental programs closely correlated with epithelial–mesenchymal transition, properties stem cells, trans-differentiation potential during exposure. From observations in various cancers, this provides an opportunity for investigating nature anticancer resistance. Over years, our understanding emerging phenotype switching modifying therapeutic response has considerably increased. This expanded knowledge contributes developing novel strategies or combination regimens using available drugs, likely improve patient outcomes clinical practice.

Language: Английский

Citations

197
Epigenetic regulation of epithelial-mesenchymal transition: focusing on hypoxia and TGF-β signaling DOI Creative Commons

Yueh-Te Lin,

Kou‐Juey Wu

Journal of Biomedical Science, Journal Year: 2020, Volume and Issue: 27(1)

Published: March 2, 2020

Abstract Epithelial-mesenchymal transition (EMT) is an important process triggered during cancer metastasis. Regulation of EMT mostly initiated by outside signalling, including TGF-β, growth factors, Notch ligand, Wnt, and hypoxia. Many signalling pathways have been delineated to explain the molecular mechanisms EMT. In this review, we will focus on epigenetic regulation two critical pathways: hypoxia TGF-β. For hypoxia, hypoxia-induced mediated interplay between chromatin modifiers histone deacetylase 3 (HDAC3) WDR5 coupled with presence lysine 4 acetylation (H3K4Ac) mark that labels promoter regions various traditional marker genes (e.g. CDH1 , VIM ). Recently identified new markers belong transcription factors SMO, GLI1) mediate themselves. TGF-β-induced ΕΜΤ, global changes, removal a variant (H2A.Z), UTX, Rad21, PRMT5, RbBP5, etc) are be crucial for both (EMT-TFs) (EMT-Ms). The utilized in these may serve as good model systems other also provide potential therapeutic targets.

Language: Английский

Citations

164