KSR1- and ERK-dependent translational regulation of the epithelial-to-mesenchymal transition

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 (...

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Autores principales:	Chaitra Rao, Danielle E Frodyma, Siddesh Southekal, Robert A Svoboda, Adrian R Black, Chittibabu Guda, Tomohiro Mizutani, Hans Clevers, Keith R Johnson, Kurt W Fisher, Robert E Lewis
Formato:	article
Lenguaje:	EN
Publicado:	eLife Sciences Publications Ltd 2021
Materias:	Human colon cancer cells human organoids Medicine R Science Q Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/88d3c636f9184176abf9681d4d5cfcad
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spelling	oai:doaj.org-article:88d3c636f9184176abf9681d4d5cfcad2021-11-16T14:16:36ZKSR1- and ERK-dependent translational regulation of the epithelial-to-mesenchymal transition10.7554/eLife.666082050-084Xe66608https://doaj.org/article/88d3c636f9184176abf9681d4d5cfcad2021-05-01T00:00:00Zhttps://elifesciences.org/articles/66608https://doaj.org/toc/2050-084XThe 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.Chaitra RaoDanielle E FrodymaSiddesh SouthekalRobert A SvobodaAdrian R BlackChittibabu GudaTomohiro MizutaniHans CleversKeith R JohnsonKurt W FisherRobert E LewiseLife Sciences Publications LtdarticleHumancolon cancer cellshuman organoidsMedicineRScienceQBiology (General)QH301-705.5ENeLife, Vol 10 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Human colon cancer cells human organoids Medicine R Science Q Biology (General) QH301-705.5
spellingShingle	Human colon cancer cells human organoids Medicine R Science Q Biology (General) QH301-705.5 Chaitra Rao Danielle E Frodyma Siddesh Southekal Robert A Svoboda Adrian R Black Chittibabu Guda Tomohiro Mizutani Hans Clevers Keith R Johnson Kurt W Fisher Robert E Lewis KSR1- and ERK-dependent translational regulation of the epithelial-to-mesenchymal transition
description	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.
format	article
author	Chaitra Rao Danielle E Frodyma Siddesh Southekal Robert A Svoboda Adrian R Black Chittibabu Guda Tomohiro Mizutani Hans Clevers Keith R Johnson Kurt W Fisher Robert E Lewis
author_facet	Chaitra Rao Danielle E Frodyma Siddesh Southekal Robert A Svoboda Adrian R Black Chittibabu Guda Tomohiro Mizutani Hans Clevers Keith R Johnson Kurt W Fisher Robert E Lewis
author_sort	Chaitra Rao
title	KSR1- and ERK-dependent translational regulation of the epithelial-to-mesenchymal transition
title_short	KSR1- and ERK-dependent translational regulation of the epithelial-to-mesenchymal transition
title_full	KSR1- and ERK-dependent translational regulation of the epithelial-to-mesenchymal transition
title_fullStr	KSR1- and ERK-dependent translational regulation of the epithelial-to-mesenchymal transition
title_full_unstemmed	KSR1- and ERK-dependent translational regulation of the epithelial-to-mesenchymal transition
title_sort	ksr1- and erk-dependent translational regulation of the epithelial-to-mesenchymal transition
publisher	eLife Sciences Publications Ltd
publishDate	2021
url	https://doaj.org/article/88d3c636f9184176abf9681d4d5cfcad
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_version_	1718426370270298112

KSR1- and ERK-dependent translational regulation of the epithelial-to-mesenchymal transition

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