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Stanniocalcin 2 (STC2) expression promotes post-radiation survival, migration and invasion of nasopharyngeal carcinoma cells

Authors He H, Qie S, Guo Q, Chen S, Zou C, Lu T, Su Y, Zong J, Xu H, He D, Xu Y, Chen B, Pan J, Sang N, Lin S

Received 10 December 2018

Accepted for publication 6 June 2019

Published 11 July 2019 Volume 2019:11 Pages 6411—6424

DOI https://doi.org/10.2147/CMAR.S197607

Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Dr Cristina Weinberg

Peer reviewer comments 3

Editor who approved publication: Professor Nakshatri


Huocong He*,1 Shuo Qie,*,2,3 Qiaojuan Guo,4 Shuyang Chen5,6 Changyan Zou,1 Tianzhu Lu,4 Ying Su,1 Jingfeng Zong,4 Hanchuan Xu,4 Dan He,5 Yun Xu,4 Bijuan Chen,4 Jianji Pan,4 Nianli Sang2,5 Shaojun Lin4

1Department of Radiation Biology, Fujian Cancer Hospital & Fujian Medical University, Fujian Provincial Key Laboratory of Translational Cancer Medicine, Fuzhou, Fujian, People’s Republic of China; 2Department of Pathology and Laboratory Medicine, Drexel University College of Medicine, Philadelphia, PA 19104, USA; 3Department of Biochemistry & Molecular Biology, Medical University of South Carolina, Charleston, SC 29425, USA; 4Department of Radiation Oncology, Fujian Cancer Hospital & Fujian Medical University, Fujian Provincial Key Laboratory of Translational Cancer Medicine, Fuzhou, Fujian, People’s Republic of China; 5Department of Biology, Drexel University College of Arts & Sciences, Philadelphia, PA 19104, USA; 6Department of Pharmacology & Experimental Therapeutics, Boston University School of Medicine, Boston, MA 02118, USA

*These authors contributed equally to this work

Background: Stanniocalcin 2 (STC2) expression is upregulated under multiple stress conditions including hypoxia, nutrient starvation and radiation. Overexpression of STC2 correlates with tumor progression and poor prognosis.
Purpose: We previously demonstrated that overexpression of STC2 in nasopharyngeal carcinomas (NPC) positively correlates with radiation resistance and tumor metastasis, two major clinical obstacles to the improvement of NPC management. However, it remains elusive whether STC2 expression is a critical contributing factor for post-radiation survival and metastasis of NPC cells.
Materials and methods: Using the radiation resistant CNE2 cell line as a model, we examined the importance of STC2 expression for post-radiation survival, migration and invasion. Here, we report the establishment of STC2 knockout lines (CNE2-STC2-KO) using the CRISPR/Cas9-based genome editing technique.
Results: Compared with the parental line, STC2-KO cells showed similar proliferation and morphology in normal culture conditions, and loss of STC2 did not compromise the cell tumorigenicity in nude mice model. However, STC2-KO lines demonstrated increased sensitivity to X-radiation under either normoxic or hypoxic conditions. Particularly, upon X-radiation, parental CNE2 cells only slightly whereas STC2-KO cells remarkably decreased the migration and invasion ability. Cell cycle analysis revealed that loss of STC2 accumulated cells in G1 and G2/M phases but decreased S-population.
Conclusion: These data indicate that the expression of STC2, which can be stimulated by metabolic or therapeutic stresses, is one important factor to promote survival and metastasis of post-radiation NPC cells. Therefore, targeting STC2 or relative downstream pathways may provide novel strategies to overcome radiation resistance and metastasis of NPC.

Keywords: metabolic stress, metastasis, migration, nasopharyngeal carcinoma, radiation resistance, stanniocalcin 2

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