Kinase inhibitor screening reveals aurora‐a kinase is a potential therapeutic and prognostic biomarker of gastric cancer

Abstract

Gastric cancer is one of the most common and deadly types of cancer in the world, and poor prognosis with treatment failure is widely reported in the literature. In this context, kinases have been considered a relevant choice for targeted therapy in gastric cancer. Here, we explore the antiproliferative and antimigratory effects of the AURKA inhibitor and the prognostic and therapeutic value as a biomarker of gastric cancer. A total of 145 kinase inhibitors were screened to evaluate the cytotoxic or cytostatic effects in the gastric cancer cell line. Using the Alamar Blue assay, flow cytometry, quantitative polymerase chain reaction, and observation of caspase 3/7 activity and cell migration, we investigated the antiproliferative, proapoptotic, and antimigratory effects of the AURKA inhibitor. Moreover, AURKA overexpression was evaluated in the gastric cell lines and the gastric tumor tissue. Out of the 145 inhibitors, two presented the highest antiproliferative effect. Both molecules can induce apoptosis by the caspases 3/7 pathway in addition to inhibiting cancer cell migration, mainly the AURKA inhibitor. Moreover, molecular docking analysis revealed that GW779439X interacts in the active site of the AURKA enzyme with similar energy as a well-described inhibitor.Our study identified AURKA overexpression in the gastric cancer cell line and gastric tumor tissue, revealing that its overexpression in patients with cancer is correlated with low survival. Therefore, it is feasible to suggest AURKA as a potential marker of gastric cancer, besides providing robust information for diagnosis and estimated survival of patients. AURKA can be considered a new molecular target used in the prognosis and therapy of gastric cancer.

Predicting AURKA as a novel therapeutic target for NPC: A comprehensive analysis based on bioinformatics and validation

“…High expression of AURKA has been reported in various tumors ( Yan et al, 2016 ; Wu et al, 2018 ; Wang-Bishop et al, 2019 ; Yi et al, 2021 ). Most notably, studies have explored the biological function of AURKA in human cancers, such as diffuse large B-cell lymphoma, glioblastoma, gastric, cervical, colorectal, and liver cancers ( Shen et al, 2019 ; Liu et al, 2021 ; Mesquita et al, 2021 ; Nguyen et al, 2021 ; Wang and Sun, 2021 ; Wu et al, 2021 ). In addition, inhibition of AURKA was shown to result in a significant reduction of GPX4 and induction of ferroptosis in tumor cells ( Gomaa et al, 2019 ).…”

Predictive and prognostic value of aurora kinase A combined with tumor-infiltrating lymphocytes in medullary thyroid carcinoma

“…The nal AURKA score of IHC was the multiple of staining intensity (0, negative; 1, weak; 2, mild; 3, strong) and staining ratio (0%, 0; 1-20%, 1; 21-50%, 2; 51-70%, 3; 81-100%, 4). Patient samples were classi ed into two groups based on high (4)(5)(6)(7)(8)(9)(10)(11)(12) and low (0-3) AURKA scores (Figures 1C).…”

“…Moreover, AURKA is closely related to disease recurrence in obese patients with early-stage breast cancer [9]. Moreover, AURKA high in patients with gastric cancer has been linked to a higher risk of death [10].…”

Pan-cancer analysis and in vitro validation of the oncogenic and prognostic roles of AURKA in human cancers

“…Aurora kinase A (AURKA) plays a crucial role as a serine/threonine kinase family member, influencing cytokinesis and spindle formation throughout the cell cycle and mitosis ( 3 , 4 ). Aberrant expression of AURKA has been observed in various human cancers, spanning gastric ( 5 ), esophageal ( 6 ), colon ( 7 ), ovarian ( 8 ), and pancreatic ( 9 ) cancers. Furthermore, elevated AURKA expression has been linked to poor prognosis and drug resistance ( 10 , 11 ).…”