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17.07.2020 | Original Article

EPAS1 promotes peritoneal carcinomatosis of non-small-cell lung cancer by enhancing mesothelial–mesenchymal transition

verfasst von: Qiang Zhen, Yaxiao Zhang, Lina Gao, Renfeng Wang, Weiwei Chu, Xiaojian Zhao, Zhe Li, Huixian Li, Bing Zhang, Baolei Lv, Jiabao Liu

Erschienen in: Strahlentherapie und Onkologie | Ausgabe 2/2021

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Abstract

Background

Non-small-cell lung cancer (NSCLC) is a major cause of cancer-related death globally. Endothelial PAS domain-containing protein 1 (EPAS1) is a homolog of the hypoxia-inducible factor 1α and has been reported to confer tyrosine kinase inhibitor (TKI) resistance in NSCLC, but its role in peritoneal carcinomatosis of NSCLC is unknown.

Methods

PC14HM, a high metastatic potential subline of NSCLC cell line PC14, was derived. Stable shRNA knockdown of EPAS1 was then established in PC14HM cells and subjected to assessment regarding the effects on proliferation and viability, xenograft tumor growth, metastatic potential, mesothelial–mesenchymal transition (MMT)-related characteristics and peritoneal carcinomatosis in a mouse model.

Results

EPAS1 expression was elevated in PC14HM cells. Knockdown of EPAS1 inhibited the proliferation and viability of PC14HM cells in vitro and suppressed tumorigenesis in vivo. In addition, the metastatic features and in vitro productions of MMT-inducing factors in PC14HM cells was also associated with EPAS1. More importantly, knockdown of EPAS1 drastically suppressed peritoneal carcinomatosis of PC14HM cells in vivo.

Conclusion

EPAS1 promotes peritoneal carcinomatosis of NSCLC through enhancement of MMT and could therefore serve as a prognostic marker or a therapeutic target in treating NSCLC, particularly in patients with peritoneal carcinomatosis.

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Titel: EPAS1 promotes peritoneal carcinomatosis of non-small-cell lung cancer by enhancing mesothelial–mesenchymal transition
verfasst von: Qiang Zhen
Yaxiao Zhang
Lina Gao
Renfeng Wang
Weiwei Chu
Xiaojian Zhao
Zhe Li
Huixian Li
Bing Zhang
Baolei Lv
Jiabao Liu
Publikationsdatum: 17.07.2020
Verlag: Springer Berlin Heidelberg
Erschienen in: Strahlentherapie und Onkologie / Ausgabe 2/2021
Print ISSN: 0179-7158
Elektronische ISSN: 1439-099X
DOI: https://doi.org/10.1007/s00066-020-01665-1

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Live-Webinar: Aktuelle Leitlinien bei Herz-Kreislauf-Erkrankungen

Springer Medizin

EPAS1 promotes peritoneal carcinomatosis of non-small-cell lung cancer by enhancing mesothelial–mesenchymal transition

Abstract

Background

Methods

Results

Conclusion

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Live-Webinar: Aktuelle Leitlinien bei Herz-Kreislauf-Erkrankungen

Springer Medizin

Abstract

Background

Methods

Results

Conclusion

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