Go to JCI Insight
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Publication alerts by email
  • Advertising
  • Job board
  • Contact
  • Clinical Research and Public Health
  • Current issue
  • Past issues
  • By specialty
    • COVID-19
    • Cardiology
    • Gastroenterology
    • Immunology
    • Metabolism
    • Nephrology
    • Neuroscience
    • Oncology
    • Pulmonology
    • Vascular biology
    • All ...
  • Videos
    • Conversations with Giants in Medicine
    • Video Abstracts
  • Reviews
    • View all reviews ...
    • Complement Biology and Therapeutics (May 2025)
    • Evolving insights into MASLD and MASH pathogenesis and treatment (Apr 2025)
    • Microbiome in Health and Disease (Feb 2025)
    • Substance Use Disorders (Oct 2024)
    • Clonal Hematopoiesis (Oct 2024)
    • Sex Differences in Medicine (Sep 2024)
    • Vascular Malformations (Apr 2024)
    • View all review series ...
  • Viewpoint
  • Collections
    • In-Press Preview
    • Clinical Research and Public Health
    • Research Letters
    • Letters to the Editor
    • Editorials
    • Commentaries
    • Editor's notes
    • Reviews
    • Viewpoints
    • 100th anniversary
    • Top read articles

  • Current issue
  • Past issues
  • Specialties
  • Reviews
  • Review series
  • Conversations with Giants in Medicine
  • Video Abstracts
  • In-Press Preview
  • Clinical Research and Public Health
  • Research Letters
  • Letters to the Editor
  • Editorials
  • Commentaries
  • Editor's notes
  • Reviews
  • Viewpoints
  • 100th anniversary
  • Top read articles
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Publication alerts by email
  • Advertising
  • Job board
  • Contact

Citations to this article

ZEB1 drives prometastatic actin cytoskeletal remodeling by downregulating miR-34a expression
Young-Ho Ahn, … , Elsa R. Flores, Jonathan M. Kurie
Young-Ho Ahn, … , Elsa R. Flores, Jonathan M. Kurie
Published August 1, 2012
Citation Information: J Clin Invest. 2012;122(9):3170-3183. https://doi.org/10.1172/JCI63608.
View: Text | PDF
Research Article Oncology Article has an altmetric score of 11

ZEB1 drives prometastatic actin cytoskeletal remodeling by downregulating miR-34a expression

  • Text
  • PDF
Abstract

Metastatic cancer is extremely difficult to treat, and the presence of metastases greatly reduces a cancer patient’s likelihood of long-term survival. The ZEB1 transcriptional repressor promotes metastasis through downregulation of microRNAs (miRs) that are strong inducers of epithelial differentiation and inhibitors of stem cell factors. Given that each miR can target multiple genes with diverse functions, we posited that the prometastatic network controlled by ZEB1 extends beyond these processes. We tested this hypothesis using a mouse model of human lung adenocarcinoma metastasis driven by ZEB1, human lung carcinoma cells, and human breast carcinoma cells. Transcriptional profiling studies revealed that ZEB1 controls the expression of numerous oncogenic and tumor-suppressive miRs, including miR-34a. Ectopic expression of miR-34a decreased tumor cell invasion and metastasis, inhibited the formation of promigratory cytoskeletal structures, suppressed activation of the RHO GTPase family, and regulated a gene expression signature enriched in cytoskeletal functions and predictive of outcome in human lung adenocarcinomas. We identified several miR-34a target genes, including Arhgap1, which encodes a RHO GTPase activating protein that was required for tumor cell invasion. These findings demonstrate that ZEB1 drives prometastatic actin cytoskeletal remodeling by downregulating miR-34a expression and provide a compelling rationale to develop miR-34a as a therapeutic agent in lung cancer patients.

Authors

Young-Ho Ahn, Don L. Gibbons, Deepavali Chakravarti, Chad J. Creighton, Zain H. Rizvi, Henry P. Adams, Alexander Pertsemlidis, Philip A. Gregory, Josephine A. Wright, Gregory J. Goodall, Elsa R. Flores, Jonathan M. Kurie

×

Total citations by year

Year: 2025 2024 2023 2022 2021 2020 2019 2018 2017 2016 2015 2014 2013 2012 Total
Citations: 2 2 6 6 12 11 11 13 7 11 8 11 8 2 110
Citation information
This citation data is accumulated from CrossRef, which receives citation information from participating publishers, including this journal. Not all publishers participate in CrossRef, so this information is not comprehensive. Additionally, data may not reflect the most current citations to this article, and the data may differ from citation information available from other sources (for example, Google Scholar, Web of Science, and Scopus).

Citations to this article in year 2014 (11)

Title and authors Publication Year
ZEB1 Sensitizes Lung Adenocarcinoma to Metastasis Suppression by PI3K Antagonism
Yanan Yang, Young-Ho Ahn, Yulong Chen, Xiaochao Tan, Lixia Guo, Don Gibbons, Christin Ungewiss, David Peng, Xin Liu, Steven Lin, Nishan Thilaganathan, Ignacio Wistuba, Jaime Rodriguez, Georgia McLendon, Chad Creighton, Jonathan Kurie
Journal of Clinical Investigation 2014
FRA-1 as a driver of tumour heterogeneity: a nexus between oncogenes and embryonic signalling pathways in cancer
AS Dhillon, E Tulchinsky
Oncogene 2014
MicroRNA in lung cancer
P Joshi
World Journal of Methodology 2014
Regulation of microRNAs in cancer metastasis
JM Bouyssou, S Manier, D Huynh, S Issa, AM Roccaro, IM Ghobrial
Biochimica et Biophysica Acta (BBA) - Reviews on Cancer 2014
MicroRNA regulation of tumorigenesis, cancer progression and interpatient heterogeneity: towards clinical use
SP Nana-Sinkam, CM Croce
Genome biology 2014
Smoking, p53 Mutation, and Lung Cancer
DL Gibbons, LA Byers, JM Kurie
Molecular cancer research : MCR 2014
Metastasis is regulated via microRNA-200/ZEB1 axis control of tumour cell PD-L1 expression and intratumoral immunosuppression
L Chen, DL Gibbons, S Goswami, MA Cortez, YH Ahn, LA Byers, X Zhang, X Yi, D Dwyer, W Lin, L Diao, J Wang, JD Roybal, M Patel, C Ungewiss, D Peng, S Antonia, M Mediavilla-Varela, G Robertson, S Jones, M Suraokar, JW Welsh, B Erez, II Wistuba, L Chen, D Peng, S Wang, SE Ullrich, JV Heymach, JM Kurie, FX Qin
Nature Communications 2014
The p53/microRNA connection in gastrointestinal cancer
H Hermeking, M Rokavec, H Li, L Jiang
Clinical and experimental gastroenterology 2014
MicroRNA and gene networks in human diffuse large B-cell lymphoma
Kunhao Wang, Zhiwen Xu, Ning Wang, Ting Xu, Minghui Zhu
Oncology Letters 2014
Mir-34: A New Weapon Against Cancer?
G Misso, MT di Martino, GD Rosa, AA Farooqi, A Lombardi, V Campani, MR Zarone, A Gullà, P Tagliaferri, P Tassone, M Caraglia
Molecular Therapy — Nucleic Acids 2014
miR-34: from bench to bedside.
Agostini M, Knight RA
Oncotarget 2014

Advertisement

Copyright © 2025 American Society for Clinical Investigation
ISSN: 0021-9738 (print), 1558-8238 (online)

Sign up for email alerts

Picked up by 1 news outlets
Posted by 2 X users
124 readers on Mendeley
1 readers on CiteULike
See more details