@article{c557d4bc5b584ad98bc1e5bfde40042e,
title = "Ksr1-and erk-dependent translational regulation of the epithelial-to-mesenchymal transition",
abstract = "rs 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.",
author = "Chaitra Rao and Frodyma, {Danielle E.} and Siddesh Southekal and Svoboda, {Robert A.} and Black, {Adrian R.} and Chittibabu Guda and Tomohiro Mizutani and Hans Clevers and Johnson, {Keith R.} and Fisher, {Kurt W.} and Lewis, {Robert E.}",
note = "Funding Information: We thank Dr. Xuan Zhang, and Dr. Kai Fu for their assistance with polysome profiling, Lisa E Humphrey-Brattain for their assistance with the colon organoid culture, the UNMC Advanced Microscopy Core, and the UNMC Cell Analysis Facility. We declare no conflicts of interest. This work was supported by P20 GM121316 (REL), and the Fred & Pamela Buffett Cancer Center Support Grant (P30 CA036727). Funding Information: We thank Dr. Xuan Zhang, and Dr. Kai Fu for their assistance with polysome profiling, Lisa E Humphrey-Brattain for their assistance with the colon organoid culture, the UNMC Advanced Microscopy Core, and the UNMC Cell Analysis Facility. We declare no conflicts of interest. This work was supported by P20 GM121316 (REL), and the Fred & Pamela Buffett Cancer Center Support Grant (P30 CA036727). The funders had no role in the study design, data collection and interpretation, or the decision to submit the work for publication. Publisher Copyright: {\textcopyright} Rao et al.",
year = "2021",
month = may,
doi = "10.7554/eLife.66608",
language = "English",
volume = "10",
pages = "1--23",
journal = "eLife",
issn = "2050-084X",
publisher = "eLife Sciences Publications",
}