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ETV5 transcriptionally activates TGFβ1 and promotes cancer cell invasion and migration of NSCLC

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Abstract

The morbidity and mortality of NSCLC remains high worldwide. However, the molecular mechanisms of NSCLC still largely unclear. Ets variant 5 (ETV5) is a transcription factor that found to be overexpressed in multiple cancers. However, the role of ETV5 in NSCLC remains unknown. We aim to explore the role and mechanisms of ETV5 in NSCLC development. The expression of ETV5 was evaluated in NSCLC tissues and cell lines. ETV5 overexpressing and downregulation cell lines were established according to the endogenous expression of ETV5. Functional studies were performed by transwell assay. The downstream targets of ETV5 were screened by PCR array and were confirmed by luciferase reporter assay. We found that overexpression of ETV5 indicates worse prognosis of NSCLC patients. Elevated ETV5 expression promotes NSCLC cell invasion and migration via transcriptional activates of TGFβ1. Therefore, ETV5/TGFβ signaling may serve as a therapeutic target for NSCLS patients.

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Abbreviations

NSCLC:

Non-small cell lung cancer

LUAD:

Lung adenocarcinoma

LUSC:

Lung squamous cell carcinoma

ETV5:

Ets variant 5

ETS:

E twenty-six

PEA3:

Polyoma enhancer activator 3

EMT:

Epithelial-mesenchymal transition

CTX:

Cetuximab

MMP2:

Matrix metalloproteinase-2

TGFβ1:

Transforming growth factor β1

NRP1:

Neuropilin-1

RCCD1:

RCC1 domain-containing protein 1

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Acknowledgements

We thank all patients who have participated in this study. We thank the members of our group participated in this work.

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Contributions

Dan Li and Yuan Wang drafted the manuscript, participated in research design, conducted experiments, and validated the data; Yanwei Shen, Hui Ren, Wang Li and Jin Yang participated in research design and conducted experiments; Yuan Wang contributed to the writing of the manuscript, discussing data and supervised the study. All authors performed data analysis and interpretation and read and approved the final manuscript.

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Correspondence to Yuan Wang.

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The authors declare no competing interests.

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Li, D., Shen, Y., Ren, H. et al. ETV5 transcriptionally activates TGFβ1 and promotes cancer cell invasion and migration of NSCLC. J Mol Histol 54, 419–426 (2023). https://doi.org/10.1007/s10735-023-10148-3

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  • DOI: https://doi.org/10.1007/s10735-023-10148-3

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