Upregulation of S100A6 in patients with endometriosis and its role in ectopic endometrial stromal cells

Abstract

S100 calcium-binding protein A6 (S100A6) is up-regulated in many malignancies and overexpression of S100A6 has been identified associated with proliferation, migration and invasion phenotype in several cancer cells. In the present study, we explored whether S100A6 plays a role in the development of endometriosis. Significantly higher levels of mRNA and protein expression of S100A6 were observed in ectopic endometrial tissues compared to eutopic and normal endometrial tissues. Silencing of S100A6 in ectopic endometrial stromal cells (ESCs) significantly inhibited cell viability, migration and invasion. Moreover, knockdown of S100A6 suppressed p38/MAPK activity in ectopic ESCs, which can be partially attenuated by CacyBP/SIP phosphorylation inhibitor. In conclusion, our results suggest that the abnormal expression of S100A6 may contribute to the pathogenesis of endometriosis and the S100A6/CacyBP/p38 signaling may provide as a promising treatment target.

Chinese abstract

S100钙结合蛋白A6（S100A6）在很多恶性疾病中是上调的, 并且S100A6的过度表达已被证实与增生、转移和几种肿瘤细胞的入侵表型有关。在本研究中, 我们探索S100A6在子宫内膜异位症的发展中是否起作用。与正位并正常的子宫内膜组织相比, 异位子宫内膜组织中mRNA水平及S100A6的表达明显增高。异位子宫内膜基质细胞中S100A6的沉默明显抑制了细胞活性、转移和侵袭力。而且, 敲除异位子宫内膜基质细胞中的S100A6, 抑制了p38/MAP激酶活性, 这可被CacyBP/SIP磷酸化抑制剂部分减弱。结论中, 我们的结果表明了S100A6的异常表达可能会促进子宫内膜异位症的发病机制, 以及S100A6/CacyBP/p38信号可能是一个有前景的治疗靶点。

Keywords:

• Endometriosis
• S100A6
• ectopic endometrial stromal cells
• CacyBP/SIP
• MAPK

Disclosure statement

The authors report no conflicts of interest.

Additional information

Funding

This study was supported by grants from the National Natural Science Foundation of China [No. 81370694] and the Science and Technology Foundation of Zhejiang Province [No. 2015C33110].