TGF-β-mediated Epithelial-mesenchymal Transition and Tumor-promoting Effects in CMT64 Cells Are Reflected in the Transcriptomic Signature of Human Lung Adenocarcinoma

Overview

Journal Sci Rep

Specialty Science

Date 2021 Nov 18

PMID 34789779

Citations 3

Authors

Naoya Miyashita

Takayoshi Enokido

Masafumi Horie

Kensuke Fukuda

Hirokazu Urushiyama

Carina Strell

Hans Brunnstrom

Patrick Micke

Akira Saito

Takahide Nagase

Affiliations

Soon will be listed here.

Abstract

Epithelial-mesenchymal transition (EMT) is a cellular process during which epithelial cells acquire mesenchymal phenotypes. Cancer cells undergo EMT to acquire malignant features and TGF-β is a key regulator of EMT. Here, we demonstrate for the first time that TGF-β could elicit EMT in a mouse lung adenocarcinoma cell line. TGF-β signaling activation led to cell morphological changes corresponding to EMT and enhanced the expression of mesenchymal markers and EMT-associated transcription factors in CMT64 lung cancer cells. RNA-sequencing analyses revealed that TGF-β increases expression of Tead transcription factors and an array of Tead2 target genes. TGF-β stimulation also resulted in alternative splicing of several genes including Cd44, tight junction protein 1 (Tjp1), and Cortactin (Cttn). In parallel with EMT, TGF-β enhanced cell growth of CMT64 cells and promoted tumor formation in a syngeneic transplantation model. Of clinical importance, the expression of TGF-β-induced genes identified in CMT64 cells correlated with EMT gene signatures in human lung adenocarcinoma tissue samples. Furthermore, TGF-β-induced gene enrichment was related to poor prognosis, underscoring the tumor-promoting role of TGF-β signaling in lung adenocarcinoma. Our cellular and syngeneic transplantation model would provide a simple and useful experimental tool to study the significance of TGF-β signaling and EMT.

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