Products Cited in Publications Worldwide KLF5 inhibition initiates epithelial-mesenchymal transition in non-transformed human squamous epithelial cells

KLF5 inhibition initiates epithelial-mesenchymal transition in non-transformed human squamous epithelial cells

Dharmendra Bhargava; David Rusakow; Wilson Zhang; Silina Awad; Jonathan P. Katz

DOI: PMID:

Abstract

The transcriptional regulator Krüppel -like factor 5 (KLF5 ) is highly expressed in squamous epithelial cells of the esophagus. Increased KLF5 activity induce s tumorigenesis and promotes metastasis in several cancers, although this function appears to be context -dependent. Here, we demonstrate that acute KLF5 inhibition, both genetically and with the potent KLF5 inhibitor ML264, causes non -transformed human primary esophageal squamous epithelial cells to enter the epithelial to mesenchymal transition (EMT). Moreover, chronic KLF5 inhibition with ML264 leads to the development of cells with a mesenchymal phenotype characterized by the expression of mesenchymal markers and functionally by reduced cell growth and increased migration and cellular invasion. This EMT resulting from chronic KLF5 inhibition is not driven by β -Catenin or TGF -β signaling. Pharmacologically, ML264 inhibits KLF5 by promoting proteasomal -mediated degradation. Taken together, we demonstrate that reduced KLF5 activity reprogram s epithelial cells towards a mesenchymal phenotype and enhance s their migratory and invasive potential. These findings have potential implications not only for esophageal cancer s but also for normal processes such as esophageal tissue repair following injury.

Keywords

KLF5 ; EMT ; epithelial ; migration ; invasion

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SR18662

A14937942505001-62-595%

SR18662

359.0/100mg

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