Epithelial–mesenchymal plasticity in carcinoma metastasis
Jeff H. Tsai,Jing Yang +1 more
TLDR
The functional requirement of EMT and/or MET during the individual steps of tumor metastasis is reviewed and the potential of targeting this program when treating metastatic diseases is discussed.Abstract:
Tumor metastasis is a multistep process by which tumor cells disseminate from their primary site and form secondary tumors at a distant site. Metastasis occurs through a series of steps: local invasion, intravasation, transport, extravasation, and colonization. A developmental program termed epithelial-mesenchymal transition (EMT) has been shown to play a critical role in promoting metastasis in epithelium-derived carcinoma. Recent experimental and clinical studies have improved our knowledge of this dynamic program and implicated EMT and its reverse program, mesenchymal-epithelial transition (MET), in the metastatic process. Here, we review the functional requirement of EMT and/or MET during the individual steps of tumor metastasis and discuss the potential of targeting this program when treating metastatic diseases.read more
Citations
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The RNA binding protein quaking regulates formation of circRNAs.
Simon J. Conn,Katherine A. Pillman,Katherine A. Pillman,John Toubia,John Toubia,Vanessa M. Conn,Marika Salmanidis,Caroline A Phillips,Caroline A Phillips,Suraya Roslan,Andreas W. Schreiber,Andreas W. Schreiber,Andreas W. Schreiber,Philip A. Gregory,Philip A. Gregory,Gregory J. Goodall,Gregory J. Goodall +16 more
TL;DR: It is shown that hundreds of circRNAs are regulated during human epithelial-mesenchymal transition (EMT) and that the production of over one-third of abundant circ RNAs is dynamically regulated by the alternative splicing factor, Quaking (QKI), which itself is regulated during EMT.
Journal ArticleDOI
Signaling mechanisms of the epithelial-mesenchymal transition
TL;DR: This review discusses how intracellular pathways and extracellular signals that regulate gene expression to induce EMT crosstalk and respond to signals from the microenvironment to regulate the expression and function of EMT-inducing transcription factors in development, physiology, and disease.
Journal ArticleDOI
Guidelines and definitions for research on epithelial–mesenchymal transition
Jing Yang,Parker B. Antin,Geert Berx,Cédric Blanpain,Thomas Brabletz,Marianne E. Bronner,Kyra Campbell,Amparo Cano,Jordi Casanova,Gerhard Christofori,Shoukat Dedhar,Rik Derynck,Heide L. Ford,Jonas Fuxe,Antonio García de Herreros,Gregory J. Goodall,Anna-Katerina Hadjantonakis,Ruby Yun-Ju Huang,Chaya Kalcheim,Raghu Kalluri,Yibin Kang,Yeesim Khew-Goodall,Herbert Levine,Jinsong Liu,Gregory D. Longmore,Sendurai A. Mani,Joan Massagué,Roberto Mayor,David R. McClay,Keith E. Mostov,Donald F. Newgreen,M. Angela Nieto,Alain Puisieux,Alain Puisieux,Raymond B. Runyan,Pierre Savagner,Ben Z. Stanger,Marc P. Stemmler,Yoshiko Takahashi,Masatoshi Takeichi,Eric Theveneau,Jean Paul Thiery,Erik W. Thompson,Robert A. Weinberg,Elizabeth D. Williams,Jianhua Xing,Binhua P. Zhou,Guojun Sheng +47 more
TL;DR: This Consensus Statement is the outcome of a 2-year-long discussion among EMT researchers and aims to both clarify the nomenclature and provide definitions and guidelines for EMT research in future publications to reduce misunderstanding and misinterpretation of research data generated in various experimental models.
Journal ArticleDOI
The Immunomodulatory and Anti-Inflammatory Role of Polyphenols.
TL;DR: It is shown that polyphenols can play a beneficial role in the prevention and the progress of chronic diseases related to inflammation such as diabetes, obesity, neurodegeneration, cancers, and cardiovascular diseases, among other conditions.
Journal ArticleDOI
Metastasis is regulated via microRNA-200/ZEB1 axis control of tumour cell PD-L1 expression and intratumoral immunosuppression
Limo Chen,Don L. Gibbons,Sangeeta Goswami,Maria Angelica Cortez,Young Ho Ahn,Lauren Averett Byers,Xuejun Zhang,Xiaohui Yi,David Dwyer,Wei Lin,Lixia Diao,Jing Wang,Jonathon D. Roybal,Mayuri Patel,Christin Ungewiss,David H. Peng,Scott J. Antonia,Melanie Mediavilla-Varela,Gordon Robertson,Steve Jones,Milind Suraokar,James W. Welsh,Baruch Erez,Ignacio I. Wistuba,Lieping Chen,Di Peng,Shanshan Wang,Stephen E. Ullrich,John V. Heymach,Jonathan M. Kurie,F. Xiao Feng Qin,F. Xiao Feng Qin +31 more
TL;DR: A molecular link between epithelial-to-mesenchymal transition (EMT) and CD8+ TIL immunosuppression and cancer progression is demonstrated and ZEB1 promotes metastasis through a heretofore unappreciated cell non-autonomous mechanism, and subgroups of patients in whom malignant progression is driven by EMT activators may respond to treatment with PD-L1 antagonists.
References
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The transcription factor Snail controls epithelial–mesenchymal transitions by repressing E-cadherin expression
Amparo Cano,Mirna Perez-Moreno,Isabel Rodrigo,Annamaria Locascio,Maria Blanco,Marta G. del Barrio,Francisco Portillo,M. Angela Nieto +7 more
TL;DR: It is shown that mouse Snail is a strong repressor of transcription of the E-cadherin gene, opening up new avenues for the design of specific anti-invasive drugs.
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The transcription factor snail is a repressor of E-cadherin gene expression in epithelial tumour cells.
Eduard Batlle,Elena Sancho,Clara Francí,David Domı́nguez,Mercè Monfar,Josep Baulida,Antonio García de Herreros +6 more
TL;DR: It is shown that the transcription factor Snail, which is expressed by fibroblasts and some E-cadherin-negative epithelial tumour cell lines, binds to three E-boxes present in the human E-CADherin promoter and represses transcription of E- cadhersin.
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Identification of Selective Inhibitors of Cancer Stem Cells by High-Throughput Screening
Piyush Gupta,Piyush Gupta,Tamer T. Onder,Guozhi Jiang,Guozhi Jiang,Kai Tao,Charlotte Kuperwasser,Robert A. Weinberg,Eric S. Lander +8 more
TL;DR: Global gene expression analyses show that salinomycin treatment results in the loss of expression of breast CSC genes previously identified by analyses of breast tissues isolated directly from patients, demonstrating the ability to identify agents with specific toxicity for epithelial CSCs.
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The miR-200 family determines the epithelial phenotype of cancer cells by targeting the E-cadherin repressors ZEB1 and ZEB2
TL;DR: In this article, the miR-200 miRNA family was found to directly target the mRNA of the E-cadherin transcriptional repressors ZEB1 (TCF8/δEF1) and ZEB2 (SMAD-interacting protein 1 [SIP1]/ZFXH1B).
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Regulatory networks defining EMT during cancer initiation and progression
Bram De Craene,Geert Berx +1 more
TL;DR: The EMT-associated reprogramming of cells not only suggests that fundamental changes may occur to several regulatory networks but also that an intimate interplay exists between them.