ELF-1 expression in nasopharyngeal carcinoma facilitates proliferation and metastasis of cancer cells via modulation of CCL2/CCR2 signaling
Authors Chen CH, Su LJ, Tsai HT, Hwang CF
Received 28 November 2018
Accepted for publication 16 April 2019
Published 6 June 2019 Volume 2019:11 Pages 5243—5254
Checked for plagiarism Yes
Review by Single-blind
Peer reviewer comments 2
Editor who approved publication: Dr Antonella D'Anneo
Chang-Han Chen,1,2 Li-Jen Su,3–5 Hsin-Ting Tsai,1 Chung-Feng Hwang6,7
1Guangdong Institute of Gastroenterology, Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Disease, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510020, People’s Republic of China; 2Department of Applied Chemistry, Graduate Institute of Biomedicine and Biomedical Technology, National Chi Nan University, Nantou, 54561, Taiwan; 3Department of Biomedical Sciences and Engineering, College of Health Sciences and Technology, National Central University, Taoyuan City, Taiwan; 4Education and Research Center for Technology Assisted Substance Abuse Prevention and Management, Taoyuan City, Taiwan; 5IHMed Global, Taipei City, Taiwan; 6Department of Otolaryngology, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Kaohsiung, 83301, Taiwan; 7Kaohsiung Chang Gung Head and Neck Oncology Group, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung 83301, Taiwan
Background: Nasopharyngeal carcinoma (NPC) is a prevalent malignant tumor in Southeast Asia. The management of NPC has remained a challenge until now. ELF-1 is a member of the ETS family of transcription factors that regulate genes involved in cellular growth. ELF-1 expression has been reported in various cancers and is required for tumor growth and angiogenesis; however, its function in NPC remains unclear. In the present study, we characterized the role and underlying mechanism of ELF-1 in NPC.
Methods: The biological functions of ELF-1 in NPC cells such as proliferation, migration, invasion, and drug resistance were investigated using MTT, BrdU incorporation, and Transwell assays. To gain more insight into the mechanism of ELF-1 in NPC, we analyzed CCL2/CCR2 signaling by Western blotting, ELISA, siRNAs, and CCR2 antagonist.
Results: Gain-of-function of ELF-1 in TW01 and TW04 cells promoted NPC cell proliferation, BrdU incorporation, migration, invasion and cisplatin resistance. By contrast, knockdown of ELF-1 produced opposite results. Overexpression of ELF-1 enhanced the expression of CCL2 via binding to its promoter region and increased the level of the extracellular matrix protein CCL2 in cell culture medium. ELF-1 expression also modulated the downstream targets of CCL2/CCR2 signaling. Most importantly, ELF-1-induced NPC malignant phenotypes were abrogated by a CCR2 inhibitor, implying that the CCL2/CCR2 signaling axis was involved in ELF-1-mediated regulation in NPC.
Conclusion: Our data suggest that ELF-1 plays an oncogenic role in NPC development associated with the CCL2/CCR2 signaling pathway and may therefore be a potential target for NPC therapy.
Keywords: ELF-1, NPC, CCL2
This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution - Non Commercial (unported, v3.0) License. By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms.Download Article [PDF] View Full Text [HTML][Machine readable]