S100A16 induces epithelial-mesenchymal transition in human PDAC cells and is a new therapeutic target for pancreatic cancer treatment that synergizes with gemcitabine.

Biochem Pharmacol

Department of Abdominal Oncology, The Cancer Center of the Fifth Affiliated Hospital, Sun Yat-sen University, Zhuhai, Guangdong Province 519000, China. Electronic address:

Published: July 2021

Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal cancers, with a poor 5-year survival rate of approximately 6%, mostly due to poor treatment response and early progression. The S100 gene family participates in various pathophysiological processes in various malignancies. S100A16 is a member of the S100 family, which is abnormally expressed in PDAC; however, its biological functions and mechanisms of action remain unclear. We analysed the Gene Expression Omnibus (GEO) public database and the gene ChIP data collected in our previous study of human PDAC cell line PANC-1 cocultured with M2 macrophages to identify differentially expressed genes (DEGs). Twenty-three overexpressed genes were identified by screening. Then, the selected genes were analysed using The Cancer Genome Atlas (TCGA) database to assess whether they have significant impact on the overall survival (OS) of PDAC patients. Of the 14 DEGs identified, S100A16 was associated with poor prognosis and was selected for further investigation; the results indicate that S100A16 is positively correlated with epithelial-mesenchymal transition (EMT)-related genes in the TCGA dataset. Subsequent in vitro and in vivo experiments demonstrated that S100A16 induces the EMT to promote the metastasis of human PDAC cells and that the effect is mediated by the enhanced expression of TWIST1 and activation of the STAT3 signalling pathway. The antitumour effect of gemcitabine (GEM) was enhanced in combination with S100A16 downregulation. In conclusion, our findings suggest that S100A16 is a novel potential therapeutic target for human PDAC treatment.

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.bcp.2020.114396DOI Listing

Publication Analysis

Top Keywords

human pdac
16
s100a16 induces
8
epithelial-mesenchymal transition
8
pdac cells
8
therapeutic target
8
s100a16
7
pdac
7
induces epithelial-mesenchymal
4
human
4
transition human
4

Similar Publications

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!