The overexpression of Aurora kinase A (AURKA) promotes the progression of gastrointestinal stromal tumor (GIST) and enhances imatinib resistance, according to a new study published in Cancer Cell International. This means AURKA could be a potential therapeutic target for GISTs.
GIST is a common tumor originating from the mesenchyme of the digestive system with unique malignant behaviors. Imatinib treatment can improve prognosis in patients with GIST, but the efficacy of the treatment is limited in eliminating mature GIST cells and about 85%–90% of patients experience disease progression due to acquired resistance to imatinib within 2 years.
To identify new targets that may play a role in the progression of GIST and confer imatinib resistance to GIST cells, a team of researchers in China led by Weilin Wang, MD, analyzed differences in gene expression profiles between advanced and nonadvanced GISTs. They then constructed a protein-protein interaction network to identify potential target genes that may play a role in the progression of the disease.
Using this approach, the researchers identified 606 differentially expressed genes between advanced and nonadvanced GISTs. They found the genes that were upregulated in advanced GISTs were mainly involved in cell division. Using bioinformatic tools, the researchers identified AURKA as an intersecting hub gene.
AURKA is a member of a family of mitotic serine/threonine kinases which is involved in the cell cycle. Using data from the GEPIA database, a newly developed web server for cancer and normal gene expression profiling and interactive analysis, the researchers found that the expression of AURKA is elevated in many other human digestive malignancies, including stomach carcinoma, liver hepatocellular carcinoma, and colorectal carcinoma.
To understand the role of AURKA in cell proliferation, apoptosis, and possibly imatinib resistance in GISTs, the researchers overexpressed it in a GIST cell culture. They found that the overexpression of AURKA significantly enhanced cell proliferation and this persisted even in the presence of imatinib. Moreover, AURKA overexpression markedly suppressed apoptosis in the cell culture with or without imatinib.
“The results suggested that AURKA overexpression enhanced the resistance of GIST cells to imatinib,” the researchers wrote, adding that AURKA is a potential therapeutic target for GISTs. Further experiments are needed to investigate the potential of AURKA-targeted therapies in GIST.
Cheng X, Wang J, Lu S, Fan W, Wang W. Aurora kinase A (AURKA) promotes the progression and imatinib resistance of advanced gastrointestinal stromal tumors. Cancer Cell Int. 2021;31;21(1):407. doi:10.1186/s12935-021-02111-7