Interferon-induced transmembrane protein 1-mediated EGFR/SOX2 signaling axis is essential for progression of non-small cell lung cancer
- 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.
- All Author(s)
- Y. G. Yang
; Y. W. Koh
; I. N. Sari
; N. Jun
; S. Lee
; L. T. H. Phi
; K. S. Kim
; Y. T. Wijaya
; S. H. Lee
; M. J. Baek
; D. Jeong
; H. Y. Kwon
- Issued Date
- 2019
- Type
- Article
- Keyword
- Adenocarcinoma of Lung/mortality/*pathology; Adult; Aged; Aged, 80 and over; Animals; Antigens, Differentiation/genetics/*metabolism; Carcinoma, Non-Small-Cell Lung/mortality/*pathology; Cell Line, Tumor; Disease Progression; ErbB Receptors/metabolism; Female; *Gene Expression Regulation, Neoplastic; Humans; Lung/pathology; Lung Neoplasms/mortality/*pathology; Male; Mice, Inbred NOD; Middle Aged; RNA, Small Interfering/metabolism; Retrospective Studies; SOXB1 Transcription Factors/metabolism; Signal Transduction; Survival Analysis; Xenograft Model Antitumor Assays; Csc; Egfr; Emt; Ifitm1; Nsclc; Sox2; adenocarcinoma
- Publisher
- Fundação Calouste Gulbenkian
International Union against Cancer
National Institutes of Health
- ISSN
- 0020-7136
- Citation Title
- International Journal of Cancer
- Citation Volume
- 144
- Citation Number
- 8
- Citation Start Page
- 2020
- Citation End Page
- 2032
- Language(ISO)
- eng
- DOI
- 10.1002/ijc.31926
- URI
- http://schca-ir.schmc.ac.kr/handle/2022.oak/3268
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