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KSR1 和 ERK 依赖性调控上皮-间质转化的翻译。

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

机构信息

Eppley Institute, University of Nebraska Medical Center, Omaha, United States.

Department of Genetics, Cell Biology and Anatomy, University of Nebraska Medical Center, Omaha, United States.

出版信息

Elife. 2021 May 10;10:e66608. doi: 10.7554/eLife.66608.

DOI:10.7554/eLife.66608
PMID:33970103
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8195604/
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.

摘要

上皮-间质转化 (EMT) 被认为是一种转录过程，它诱导细胞从极化状态向迁移表型转变。在这里，我们表明 KSR1 和 ERK 通过优先翻译上皮-间质相互作用 1 (EPSTI1) 来促进 EMT 样表型，这对于诱导从 E-到 N-钙粘蛋白的转变以及协调迁移和侵袭行为是必需的。EPSTI1 在人结直肠癌 (CRC) 细胞中过表达。KSR1 或 EPSTI1 的破坏显著抑制体外细胞迁移和侵袭，并通过降低 N-钙粘蛋白和 E-钙粘蛋白表达的转录抑制因子 ZEB1 和 Slug 的表达，部分逆转 EMT 样表型。在缺乏 KSR1 的 CRC 细胞中，异位 EPSTI1 表达恢复了 E-到 N-钙粘蛋白的转变、迁移、侵袭和锚定非依赖性生长。KSR1 通过选择性翻译 mRNA 诱导 EMT 样表型，揭示了其在重塑 CRC 细胞翻译景观以促进其迁移和侵袭行为方面的作用被低估。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/421a/8195604/4cd2c4d81db7/elife-66608-sa2-fig1.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/421a/8195604/2c88db0cd0f4/elife-66608-fig7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/421a/8195604/4cd2c4d81db7/elife-66608-sa2-fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/421a/8195604/1899f69cfd97/elife-66608-fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/421a/8195604/737455b64956/elife-66608-fig1-figsupp1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/421a/8195604/651bdc2c5607/elife-66608-fig1-figsupp2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/421a/8195604/fc8fdbf46abf/elife-66608-fig2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/421a/8195604/fbe5c381b4ed/elife-66608-fig3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/421a/8195604/c45cd186301e/elife-66608-fig4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/421a/8195604/2c2e652ee879/elife-66608-fig5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/421a/8195604/63c35ca85123/elife-66608-fig5-figsupp1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/421a/8195604/c5e93b0e9e2f/elife-66608-fig6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/421a/8195604/76a4e51f0c7a/elife-66608-fig6-figsupp1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/421a/8195604/2c88db0cd0f4/elife-66608-fig7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/421a/8195604/4cd2c4d81db7/elife-66608-sa2-fig1.jpg

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