USP1 links platinum resistance to cancer cell dissemination by regulating Snail stability DOI Creative Commons
Maura Sonego, Ilenia Pellarin, Alice Costa

et al.

Science Advances, Journal Year: 2019, Volume and Issue: 5(5)

Published: May 3, 2019

Resistance to platinum-based chemotherapy is a common event in patients with cancer, generally associated tumor dissemination and metastasis. Whether platinum treatment per se activates molecular pathways linked spreading not known. Here, we report that the ubiquitin-specific protease 1 (USP1) mediates ovarian cancer cell resistance platinum, by regulating stability of Snail, which, turn, promotes dissemination. At level, observed upon treatment, USP1 phosphorylated ATM ATR binds Snail. Then, de-ubiquitinates stabilizes Snail expression, conferring increased stem cell-like features, metastatic ability. Consistently, knockout or pharmacological inhibition sensitivity decreased Snail-dependent manner. Our findings identify as target open way novel strategy overcome more successfully treat cancer.

Language: Английский

Inflammation and Cancer: Triggers, Mechanisms, and Consequences DOI Creative Commons
Florian R. Greten, Sergei I. Grivennikov

Immunity, Journal Year: 2019, Volume and Issue: 51(1), P. 27 - 41

Published: July 1, 2019

Language: Английский

Citations

2786
Phenotypic Plasticity: Driver of Cancer Initiation, Progression, and Therapy Resistance DOI Creative Commons

Piyush B. Gupta,

Ievgenia Pastushenko,

Adam Skibinski

et al.

Cell stem cell, Journal Year: 2018, Volume and Issue: 24(1), P. 65 - 78

Published: Dec. 13, 2018

Language: Английский

Citations

502
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

490
Non-redundant functions of EMT transcription factors DOI
Marc P. Stemmler, Rebecca L. Eccles, Simone Brabletz

et al.

Nature Cell Biology, Journal Year: 2018, Volume and Issue: 21(1), P. 102 - 112

Published: Oct. 26, 2018

Language: Английский

Citations

464
m6A-induced lncRNA RP11 triggers the dissemination of colorectal cancer cells via upregulation of Zeb1 DOI Creative Commons
Yingmin Wu, Xiangling Yang, Zhuojia Chen

et al.

Molecular Cancer, Journal Year: 2019, Volume and Issue: 18(1)

Published: April 13, 2019

Long noncoding RNAs (lncRNAs) have emerged as critical players in cancer progression, but their functions colorectal (CRC) metastasis not been systematically clarified.lncRNA expression profiles matched normal and CRC tissue were checked using microarray analysis. The biological roles of a novel lncRNA, namely RP11-138 J23.1 (RP11), development both vitro vivo. Its association with clinical progression was further analyzed.RP11 highly expressed tissues, its increased stage patients. RP11 positively regulated the migration, invasion epithelial mesenchymal transition (EMT) cells enhanced liver Post-translational upregulation Zeb1, an EMT-related transcription factor, essential for RP11-induced cell dissemination. Mechanistically, RP11/hnRNPA2B1/mRNA complex accelerated mRNA degradation two E3 ligases, Siah1 Fbxo45, subsequently prevented proteasomal Zeb1. m6A methylation involved by increasing nuclear accumulation. Clinical analysis showed that can regulate RP11, further, Siah1-Fbxo45/Zeb1 CRC.m6A-induced lncRNA trigger dissemination via post-translational Considering high specific levels our present study paves way investigations predictive biomarker or therapeutic target CRC.

Language: Английский

Citations

331
Transforming Growth Factor-β-Induced Cell Plasticity in Liver Fibrosis and Hepatocarcinogenesis DOI Creative Commons
Isabel Fabregat, Daniel Caballero‐Díaz

Frontiers in Oncology, Journal Year: 2018, Volume and Issue: 8

Published: Sept. 10, 2018

The Transforming Growth Factor-beta (TGF-β) family plays relevant roles in the regulation of different cellular processes that are essential for tissue and organ homeostasis. In case liver, TGF-β signalling participates stages disease progression, from initial liver injury towards fibrosis, cirrhosis cancer. When a chronic takes place, mobilization lymphocytes other inflammatory cells occur, thus setting stage persistence an response. Macrophages produce profibrotic mediators, among them, TGF-β, which is responsible activation -transdifferentiation- quiescent hepatic stellate (HSC) to myofibroblast (MFB) phenotype. MFBs principal source extracellular matrix protein (ECM) accumulation prominent mediators fibrogenesis. also mediates epithelial-mesenchymal transition (EMT) process hepatocytes may contribute, directly or indirectly, increase MFB population. hepatocarcinogenesis, dual role, behaving as suppressor factor at early stages, but contributing later tumour once escape its cytostatic effects. As part potential pro-tumorigenic actions, induces EMT cells, increases pro-migratory invasive potential. parallel, changes cell plasticity, conferring properties migratory initiating (TIC). main aim this review shed light about pleiotropic actions explain effects on populations. cross-talk with pathways contribute effects, particular Epidermal Factor Receptor (EGFR), will be presented. Finally, we discuss rationale targeting pathway pathologies.

Language: Английский

Citations

279
Mesenchymal–epithelial transition in development and reprogramming DOI
Duanqing Pei, Xiaodong Shu, Ama Gassama‐Diagne

et al.

Nature Cell Biology, Journal Year: 2018, Volume and Issue: 21(1), P. 44 - 53

Published: Oct. 26, 2018

Language: Английский

Citations

253
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

196
L1CAM defines the regenerative origin of metastasis-initiating cells in colorectal cancer DOI
Karuna Ganesh,

Harihar Basnet,

Yasemin Kaygusuz

et al.

Nature Cancer, Journal Year: 2020, Volume and Issue: 1(1), P. 28 - 45

Published: Jan. 13, 2020

Language: Английский

Citations

194
Single-cell RNA-seq analysis unveils a prevalent epithelial/mesenchymal hybrid state during mouse organogenesis DOI Creative Commons
Ji Dong,

Yuqiong Hu,

Xiaoying Fan

et al.

Genome biology, Journal Year: 2018, Volume and Issue: 19(1)

Published: March 14, 2018

Organogenesis is crucial for proper organ formation during mammalian embryonic development. However, the similarities and shared features between different organs cellular heterogeneity this process at single-cell resolution remain elusive. We perform RNA sequencing analysis of 1916 individual cells from eight tissues E9.5 to E11.5 mouse embryos, namely, forebrain, hindbrain, skin, heart, somite, lung, liver, intestine. Based on regulatory activities rather than expression patterns, all analyzed can be well classified into four major groups with epithelial, mesodermal, hematopoietic, neuronal identities. For within same group, differences their developmental paths are revealed reconstructed. identify mutual interactions epithelial mesenchymal detect prevalent organogenesis, which similar intermediate epithelial/mesenchymal tumorigenesis. The comprehensive transcriptome profiled in our study paves way future mechanistic studies gene-regulatory networks governing organogenesis.

Language: Английский

Citations

179