Twist2 is NFkB-responsive when p120-catenin is inactivated and EGFR is overexpressed in esophageal keratinocytes

Heather L Lehman; Michal Kidacki; Douglas B Stairs

doi:10.1038/s41598-020-75866-0

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Twist2 is NFkB-responsive when p120-catenin is inactivated and EGFR is overexpressed in esophageal keratinocytes

Journal article

Open access

Peer reviewed

Twist2 is NFkB-responsive when p120-catenin is inactivated and EGFR is overexpressed in esophageal keratinocytes

Heather L Lehman, Michal Kidacki and Douglas B Stairs

Scientific reports, Vol.10(1), p.18829

11/02/2020

DOI: 10.1038/s41598-020-75866-0

PMCID: PMC7608670

PMID: 33139779

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Abstract

Esophageal squamous cell carcinoma (ESCC) is among the most aggressive and fatal cancer types. ESCC classically progresses rapidly and frequently causes mortality in four out of five patients within two years of diagnosis. Yet, little is known about the mechanisms that make ESCC so aggressive. In a previous study we demonstrated that p120-catenin (p120ctn) and EGFR, two genes associated with poor prognosis in ESCC, work together to cause invasion. Specifically, inactivation of p120ctn combined with overexpression of EGFR induces a signaling cascade that leads to hyperactivation of NFkB and a resultant aggressive cell type. The purpose of this present study was to identify targets that are responsive to NFkB when p120ctn and EGFR are modified. Using human esophageal keratinocytes, we have identified Twist2 as an NFkB-responsive gene. Interestingly, we found that when NFkB is hyperactivated in cells with EGFR overexpression and p120ctn inactivation, Twist2 is significantly upregulated. Inhibition of NFkB activity results in nearly complete loss of Twist2 expression, suggesting that this potential EMT-inducing gene, is a responsive target of NFkB. There exists a paucity of research on Twist2 in any cancer type; as such, these findings are important in ESCC as well as in other cancer types.

Catenins - genetics

Catenins - metabolism

Cell Line

Delta Catenin

Disease Progression

ErbB Receptors - genetics

ErbB Receptors - metabolism

Esophageal Neoplasms - genetics

Esophageal Neoplasms - pathology

Esophageal Squamous Cell Carcinoma - genetics

Esophageal Squamous Cell Carcinoma - pathology

Gene Expression

Humans

Keratinocytes - metabolism

NF-kappa B - genetics

NF-kappa B - metabolism

Repressor Proteins - genetics

Repressor Proteins - metabolism

Twist-Related Protein 1 - genetics

Twist-Related Protein 1 - metabolism

Details

Title: Subtitle: Twist2 is NFkB-responsive when p120-catenin is inactivated and EGFR is overexpressed in esophageal keratinocytes
Creators: Heather L Lehman - Millersville University
Michal Kidacki - Catholic Medical Center
Douglas B Stairs - Pennsylvania State University
Resource Type: Journal article
Publication Details: Scientific reports, Vol.10(1), p.18829
DOI: 10.1038/s41598-020-75866-0
PMID: 33139779
PMCID: PMC7608670
NLM abbreviation: Sci Rep
ISSN: 2045-2322
eISSN: 2045-2322
Language: English
Date published: 11/02/2020
Academic Unit: Dermatology
Record Identifier: 9985014709502771

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