Open Access<p>Stanniocalcin 2 (STC2) expression promotes post-radiation survival, migration and invasion of nasopharyngeal carcinoma cells</p>
Author(s) -
Hairong He,
Shuo Qie,
Qiaojuan Guo,
Shuyang Chen,
Changyan Zou,
Tianzhu Lu,
Ying Su,
Jingfeng Zong,
Xu Han,
Dan He,
Yun Xu,
Bijuan Chen,
Nianli Sang
Publication year - 2019
Publication title -
cancer management and research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.024
H-Index - 40
ISSN - 1179-1322
DOI - 10.2147/cmar.s197607
Subject(s) - nasopharyngeal carcinoma , cancer research , cell culture , biology , metastasis , downregulation and upregulation , population , radiation therapy , medicine , gene , cancer , genetics , environmental health
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 G 1 and G 2 /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.