Research Paper Volume 12, Issue 22 pp 23114—23128

Intracellular and extracellular S100A9 trigger epithelial-mesenchymal transition and promote the invasive phenotype of pituitary adenoma through activation of AKT1

Ning Huang1, , Guanjian Zhao1, , Qiang Yang1, , Jiahe Tan1, , Ying Tan2, , Jiqin Zhang3, , Yuan Cheng1, , Jin Chen1, ,

  • 1 Department of Neurosurgery, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China
  • 2 Department of Neurosurgery, Guizhou Provincial People’s Hospital, Guiyang, Guizhou, China
  • 3 Department of Anesthesiology, Guizhou Provincial People's Hospital, Guiyang, Guizhou, China

Received: June 6, 2020       Accepted: July 30, 2020       Published: November 17, 2020
How to Cite

Copyright: © 2020 Huang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.


Pituitary adenoma (PA) is mostly benign intracranial tumor, but it also displays invasive growth characteristics and provokes challenging clinical conditions. S100A9 protein enhances tumor progression. In this study, we firstly demonstrated that both intracellular and extracellular S100A9 promoted the expression of Vimentin and Intercellular cell adhesion molecule-1 (ICAM-1), coupled with reduced E-cadherin in PA. As a result, PA acquired the phenotype of Epithelial-Mesenchymal Transition (EMT), leading to proliferation, cell cycle progression, migration and invasion. In addition, we indicated S100A9-induced EMT was mediated by activation of AKT1. Furthermore, immunohistochemistry showed that S100A9 expression was higher in invasive PA than that in non-invasive PA. These data extended our understanding for the effects of S100A9 on PA invasion and contributed to further development of a promising therapeutic target for invasive PA.


CCK-8: Cell Counting Kit-8; DMEM: Dulbecco’s modified Eagle’s medium; EMT: Epithelial-Mesenchymal Transition; FBS: Fetal bovine serum; GAPDH: Glyceraldehyde-3-phosphate dehydrogenase; GFP: Green fluorescent protein; ICAM-1: Intercellular cell adhesion molecule-1; IHC: Immunohistochemistry; IPA: Invasive pituitary adenoma; MAPK: Mitogen-activated protein kinase; MDSC: Myeloid-derived suppressor cell; MEM: Minimum Essential Medium; PA: Pituitary adenoma; PBS: Phosphate buffer saline; PCR: Polymerase chain reaction; PI: Propidium iodide; PMSF: Phenylmethanesulfonyl fluoride; PVDF: Polyvinylidene fluoride; RAGE: Receptor for advanced glycation end product; shRNA: Short hairpin RNA; Thr: Threonine; TLR4: Toll-like receptor 4.