KSR1-and ERK-dependent translational regulation of the epithelial-to-mesenchymal transition
- University of Nebraska Medical Center, United States
- Royal Netherlands Academy of Arts and Sciences (KNAW) and UMC Utrecht, Netherlands
Abstract
The epithelial-to-mesenchymal transition (EMT) is considered a transcriptional process that induces a switch in cells from a polarized state to a migratory phenotype. Here we show that KSR1 and ERK promote EMT-like phenotype through the preferential translation of Epithelial-Stromal Interaction 1 (EPSTI1), which is required to induce the switch from E- to N-cadherin and coordinate migratory and invasive behavior. EPSTI1 is overexpressed in human colorectal cancer (CRC) cells. Disruption of KSR1 or EPSTI1 significantly impairs cell migration and invasion in vitro, and reverses EMT-like phenotype, in part, by decreasing the expression of N-cadherin and the transcriptional repressors of E-cadherin expression, ZEB1 and Slug. In CRC cells lacking KSR1, ectopic EPSTI1 expression restored the E- to N-cadherin switch, migration, invasion, and anchorage-independent growth. KSR1-dependent induction of EMT-like phenotype via selective translation of mRNAs reveals its underappreciated role in remodeling the translational landscape of CRC cells to promote their migratory and invasive behavior.
Data availability
The high-throughput sequencing data have been deposited in the Gene Expression Omnibus (GEO) database, www.ncbi.nlm.nih.gov/geo (accession no. GSE164492).
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Next generation sequencing analysis of control and KSR1 knockdown CRC cell line translatomes.NCBI Gene Expression Omnibus, GSE164492.
Article and author information
Author details
Funding
Nebraska center for Molecular Target Discovery and Drug Development (P20 GM121316)
- Robert E Lewis
Fred and Pamela Buffet Cancer Support Grant (P30 CA036727)
- Robert E Lewis
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Reviewing Editor
- Nahum Sonenberg, McGill University, Canada
Publication history
- Received: January 16, 2021
- Accepted: May 9, 2021
- Accepted Manuscript published: May 10, 2021 (version 1)
- Version of Record published: June 11, 2021 (version 2)
Copyright
© 2021, Rao et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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KSR1-and ERK-dependent translational regulation of the epithelial-to-mesenchymal transition
eLife 10:e66608.
https://doi.org/10.7554/eLife.66608
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