SOX2, a stemness gene, induces progression of NSCLC A549 cells toward anchorage-independent growth and chemoresistance to vinblastine
Received 30 May 2018
Accepted for publication 1 August 2018
Published 25 September 2018 Volume 2018:11 Pages 6197—6207
Checked for plagiarism Yes
Review by Single anonymous peer review
Peer reviewer comments 3
Editor who approved publication: Dr Cho
Chungyoul Choe,1,* Hyewon Kim,2,* Sol Min,2 Sangkyu Park,2,3 Jeongmin Seo,2,3 Sangho Roh2
1Samsung Biomedical Research Institute, Samsung Medical Center, Sungkyunkwan University, School of Medicine, Seoul, Republic of Korea; 2Laboratory of Cellular Reprogramming and Embryo Biotechnology, School of Dentistry, Seoul National University, Seoul, Republic of Korea; 3Biomedical Research Institute, NeoRegen Biotech Co., Ltd., Gyeonggi-do, Korea
*These authors contributed equally to this work
Background: Non-small cell lung cancer (NSCLC) is difficult to treat successfully. This intractability is mainly due to the cancer progressing through invasion, metastasis, chemotherapeutic resistance and relapse. Stemness has been linked to the various steps of cancer progression in a variety of tumors, yet little is known regarding its role in NSCLC.
Purpose: In this study, we sought to determine the role of SOX2, a master regulator of pluripotency, in the growth of extracellular matrix (ECM)-detached cells during cancer progression.
Methods: We established a three-dimensional (3D) Poly-2-hydroxyethyl methacrylate (poly-HEMA) culture of lung adenocarcinoma (LUAD) A549 cells as an ECM-detached cell growth model and examined the role of stemness genes using siRNA and small molecule inhibitor in comparison to standard two dimensional (2D) culture.
Results: In poly-HEMA culture, A549 cells formed substratum-detached spheroids with characteristics of intermediate epithelial to mesenchymal transition (EMT) and exhibited greater expression of SOX2 than did control 2D cells. Knockdown of SOX2 markedly suppressed the growth of A549 cell aggregates in poly-HEMA culture conditions and furthermore increased their sensitivity to the anticancer drug vinblastine with concomitant downregulation of the activity of the anti-apoptotic AKT kinase. Interestingly, a small molecule, RepSox, which replaces SOX2, stimulated A549 cell growth in poly-HEMA 3D culture condition.
Conclusion: Our findings strongly indicate that SOX2 contributes to anchorage-independent growth and chemoresistance via its downstream signaling mediator AKT kinase during the disease progression of NSCLC. SOX2 may therefore be an invaluable therapeutic target of NSCLC.
Keywords: SOX2, lung cancer, NSCLC, EMT, stemness, vinblastine
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