EPAS1 Promotes Peritoneal Carcinomatosis of Non-small-cell Lung Cancer by Enhancing Mesothelial-mesenchymal Transition

Overview

Journal Strahlenther Onkol

Specialties Oncology
Radiology

Date 2020 Jul 19

PMID 32681351

Citations 9

Authors

Qiang Zhen

Yaxiao Zhang

Lina Gao

Renfeng Wang

Weiwei Chu

Xiaojian Zhao

Zhe Li

Huixian Li

Bing Zhang

Baolei Lv

Jiabao Liu

Affiliations

Soon will be listed here.

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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