Interferon-induced transmembrane protein 1-mediated EGFR/SOX2 signaling axis is essential for progression of non-small cell lung cancer
- Authors
- Yang, Ying-Gui; Koh, Young Wha; Sari, Ita Novita; Jun, Nayoung; Lee, Sanghyun; Lan Thi Hanh Phi; Kim, Kwang Seock; Wijaya, Yoseph Toni; Lee, Sang Hun; Baek, Moo-Jun; Jeong, Dongjun; Kwon, Hyog Young
- Issue Date
- 15-Apr-2019
- Publisher
- John Wiley & Sons Inc.
- Keywords
- NSCLC; IFITM1; adenocarcinoma; CSC; EMT; EGFR; SOX2
- Citation
- International Journal of Cancer, v.144, no.8, pp 2020 - 2032
- Pages
- 13
- Journal Title
- International Journal of Cancer
- Volume
- 144
- Number
- 8
- Start Page
- 2020
- End Page
- 2032
- URI
- https://scholarworks.bwise.kr/sch/handle/2021.sw.sch/4581
- DOI
- 10.1002/ijc.31926
- ISSN
- 0020-7136
1097-0215
- Abstract
- Emerging data indicate that interferon-induced transmembrane protein 1 (IFITM1) plays an important role in many cancers. However, it remains unclear whether IFITM1 is functionally indispensable in nonsmall cell lung cancer (NSCLC). Here, using NSCLC cell lines and patient-derived samples, we show that IFITM1 is essentially required for the progression of NSCLC in vitro and in vivo. Specifically, IFITM1 depletion resulted in a significant reduction in sphere formation, migration, and invasion of NSCLC cells in vitro; these events were inversely correlated with the ectopic expression of IFITM1. In addition, tumor development was significantly impaired in the absence of IFITM1 in vivo. Mechanistically, epidermal growth factor receptor/sex-determining region Y-box 2 (EGFR/SOX2) signaling axis was compromised in the absence of IFITM1, and the ectopic expression of SOX2 partially rescued the defects caused by IFITM1 depletion. More importantly, using 226 patient-derived samples, we demonstrate that a high level of IFITM1 expression is associated with a poor overall survival (OS) rate in adenocarcinoma but not in squamous cell carcinoma. Collectively, these data suggest that IFITM1 is a poor prognostic marker of adenocarcinoma and an attractive target to develop novel therapeutics for NSCLC.
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- Appears in
Collections - Graduate School > Department of Integrated Biomedical Science > 1. Journal Articles
- College of Medicine > Department of Pathology > 1. Journal Articles
- College of Medicine > Department of General Surgery > 1. Journal Articles
- College of Medicine > Department of Biochemistry > 1. Journal Articles
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