TGF-β-mediated epithelial–mesenchymal transition and tumor-promoting effects in CMT64 cells are reflected in the transcriptomic signature of human lung adenocarcinoma
(2021) In Scientific Reports 11(1).- 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... (More)
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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- author
- Miyashita, Naoya ; Enokido, Takayoshi ; Horie, Masafumi ; Fukuda, Kensuke ; Urushiyama, Hirokazu ; Strell, Carina ; Brunnström, Hans LU ; Micke, Patrick ; Saito, Akira and Nagase, Takahide
- organization
- publishing date
- 2021-12
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Scientific Reports
- volume
- 11
- issue
- 1
- article number
- 22380
- publisher
- Nature Publishing Group
- external identifiers
-
- pmid:34789779
- scopus:85119293218
- ISSN
- 2045-2322
- DOI
- 10.1038/s41598-021-01799-x
- language
- English
- LU publication?
- yes
- id
- 5277ef74-bd06-452d-82ae-7fdc0a2c59f1
- date added to LUP
- 2021-12-03 15:29:26
- date last changed
- 2024-09-08 06:13:52
@article{5277ef74-bd06-452d-82ae-7fdc0a2c59f1, abstract = {{<p>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.</p>}}, author = {{Miyashita, Naoya and Enokido, Takayoshi and Horie, Masafumi and Fukuda, Kensuke and Urushiyama, Hirokazu and Strell, Carina and Brunnström, Hans and Micke, Patrick and Saito, Akira and Nagase, Takahide}}, issn = {{2045-2322}}, language = {{eng}}, number = {{1}}, publisher = {{Nature Publishing Group}}, series = {{Scientific Reports}}, title = {{TGF-β-mediated epithelial–mesenchymal transition and tumor-promoting effects in CMT64 cells are reflected in the transcriptomic signature of human lung adenocarcinoma}}, url = {{http://dx.doi.org/10.1038/s41598-021-01799-x}}, doi = {{10.1038/s41598-021-01799-x}}, volume = {{11}}, year = {{2021}}, }