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.

• Authors: Ying-Gui Yang, Young Wha Koh, Ita Novita Sari, Nayoung Jun, Sanghyun Lee, Lan Thi Hanh Phi, Kwang Seock Kim, Yoseph Toni Wijaya, Sang Hun Lee, Moo-Jun Baek, Dongjun Jeong, Hyog Young Kwon
• Journal: International journal of cancer (Int J Cancer) Vol. 144 Issue 8 Pg. 2020-2032 (04 15 2019) ISSN: 1097-0215 [Electronic] United States
• PMID: 30318841 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2018 The Authors. International Journal of Cancer published by John Wiley & Sons Ltd on behalf of UICC.

Chemical References

• Antigens, Differentiation
• RNA, Small Interfering
• SOX2 protein, human
• SOXB1 Transcription Factors
• leu-13 antigen
• EGFR protein, human
• ErbB Receptors

Topics

• 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