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

и другие.

Cell & Bioscience, Год журнала: 2022, Номер 12(1)

Опубликована: Фев. 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.

Язык: Английский

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

и другие.

Cancer Cell, Год журнала: 2020, Номер 38(2), С. 167 - 197

Опубликована: Июль 9, 2020

Язык: Английский

Процитировано

1890

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

и другие.

Nature reviews. Immunology, Год журнала: 2020, Номер 21(3), С. 151 - 161

Опубликована: Авг. 24, 2020

Язык: Английский

Процитировано

572

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

Yuhe Huang,

Weiqi Hong,

Xiawei Wei

и другие.

Journal of Hematology & Oncology, Год журнала: 2022, Номер 15(1)

Опубликована: Сен. 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.

Язык: Английский

Процитировано

523

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

Nature reviews. Cancer, Год журнала: 2021, Номер 21(5), С. 325 - 338

Опубликована: Фев. 5, 2021

Язык: Английский

Процитировано

413

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

и другие.

Molecular Cancer, Год журнала: 2020, Номер 19(1)

Опубликована: Май 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.

Язык: Английский

Процитировано

266

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

и другие.

Frontiers in Oncology, Год журнала: 2020, Номер 10

Опубликована: Апрель 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.

Язык: Английский

Процитировано

235

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

и другие.

Genome Medicine, Год журнала: 2020, Номер 12(1)

Опубликована: Сен. 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

Язык: Английский

Процитировано

219

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

и другие.

Cancer Cell, Год журнала: 2020, Номер 37(2), С. 168 - 182.e4

Опубликована: Янв. 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

Язык: Английский

Процитировано

201

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

и другие.

Signal Transduction and Targeted Therapy, Год журнала: 2020, Номер 5(1)

Опубликована: Окт. 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.

Язык: Английский

Процитировано

198

Tumor biomarkers for diagnosis, prognosis and targeted therapy DOI Creative Commons
Yue Zhou, Lei Tao, Jiahao Qiu

и другие.

Signal Transduction and Targeted Therapy, Год журнала: 2024, Номер 9(1)

Опубликована: Май 20, 2024

Abstract Tumor biomarkers, the substances which are produced by tumors or body’s responses to during tumorigenesis and progression, have been demonstrated possess critical encouraging value in screening early diagnosis, prognosis prediction, recurrence detection, therapeutic efficacy monitoring of cancers. Over past decades, continuous progress has made exploring discovering novel, sensitive, specific, accurate tumor significantly promoted personalized medicine improved outcomes cancer patients, especially advances molecular biology technologies developed for detection biomarkers. Herein, we summarize discovery development including history conventional innovative used biomarker classification biomarkers based on tissue origins, application clinical management. In particular, highlight recent advancements biomarker-based anticancer-targeted therapies emerging as breakthroughs promising strategies. We also discuss limitations challenges that need be addressed provide insights perspectives turn into opportunities this field. Collectively, multiple emphasized review may guidance precision medicine, broaden horizons future research directions, expedite patients according their rather than organs origin.

Язык: Английский

Процитировано

179