Aurora kinase A induces chemotherapy resistance through revival of dormant cells in laryngeal squamous cell carcinoma

Abstract

Background: Chemotherapy resistance was an important tumor metastasis mechanism. Methods: Cell Counting Kit-8 assay and plate colony formation assay were applied to examine the proliferation of laryngeal squamous cell carcinoma (LSCC). Immunofluorescent staining and Western blotting were carried out to show the expression of related proteins. Wound healing, migration, and invasion assays were used to examine the mobility, migration, and invasion of LSCC. Results: Downregulated Aurora kinase A (AURKA) increased chemotherapy sensitivity and reduced the ability of mobility, migration, and invasion of Hep2 cells, while upregulated AURKA possessed opposite results. Hep2/5-Fu cells possessed dormancylike properties and upregulated AURKA in Hep2/5-Fu cells (Hep2/5-Fu/AURKA cells) revived dormant state. Furthermore, Erk1/2 was restrained in Hep2/5-Fu cells and activated in Hep2/5-Fu/AURKA cells. Moreover, Erk1/2 accelerated the ability of mobility, migration, and invasion in Hep2/5-Fu/AURKA cells. Conclusion: AURKA activated dormant state to induce chemotherapy resistance and promoted metastasis of LSCC through Erk1/2 pathway.Laryngeal squamous cell carcinoma (LSCC), arisen from the larynx epithelium, is one of the most common cancer worldwide. 1 Despite the improvement of current chemotherapy, surgery, and radiotherapy, the 5-year survival rate of LSCC is only approximately 60%. 2 The main death cause of LSCC is metastasis and relapse. 3 Therefore，elucidating molecular mechanisms to design novel strategies is very essential for improving survival of LSCC.Chemotherapy is usually used in the neoadjuvant, adjuvant, or primary treatment options of advanced LSCC. 4 The common chemotherapeutic drugs use for the treatment of LSCC which includes Fluorouracil (5-Fu), placetatin, taxel, gemzar and cisplatin. Among them, 5-Fu has been used for the treatment of head and neck, gastric, breast, and colorectal cancers. 5 Despite the fact that the effect of these chemotherapeutic drugs is prominent, chemotherapy resistance of cancers is the main cause of relapse and mortality. 6,7 Thus, it is essential to research new targets to improve the chemotherapy effect of LSCC.Aurora kinase A (AURKA) is a homolog of aurora/ Ipl1-related kinase which is located at chromosome 20q13.2. 8 More and more researchers had proved AURKA, an oncogene, contributed to plenty of malignant cancers, including head and neck, bladder, ovarian, colon, breast, and pancreatic cancers. 3,[9][10][11][12][13] In our previous study, AURKA was overexpressed in LSCC and associated with regional lymph node metastasis and late clinical stage. 3 Moreover, AURKA might activate dormant state to promote the metastasis of Li-yun Yang and Ya-min Shan contributed equally to this article.

AlG3 Induces AURKA to Promote Laryngeal Squamous Cell Carcinoma Metastasis

“…AURKA is frequently ampli ed and/or overexpressed in GI malignancies (including esophageal, gastric, and colorectal and head and neck cancers) [16][17][18][19] . Our previous research found Aurora kinase A (AURKA) revives dormant LSCC to promote LSCC metastasis 3,5 . Therefore, illustrating speci c molecular mechanism of AURKA revives dormant LSCC to promote LSCC metastasis was of great concern.…”

“…Our previous research found Aurora kinase A (AURKA) revives dormant LSCC to promote metastasis 3,5 . Therefore, illustrating speci c molecular mechanism of AURKA revives dormant LSCC to promote metastasis was of great concern.…”

AlG3 Induces AURKA to Promote Laryngeal Squamous Cell Carcinoma Metastasis

“…AURKA is frequently ampli ed and/or overexpressed in GI malignancies (including esophageal, gastric, and colorectal and head and neck cancers) [16][17][18][19] . Our previous research found Aurora kinase A(AURKA) revives dormant LSCC to promote LSCC metastasis 3,5 .Therefore, illustrating speci c molecular mechanism of AURKA revives dormant LSCC to promote LSCC metastasiswas of great concern. The key moleculesmaybe capable to potential prognostic value and potential targets for clinical LSCC treatment.…”

“…Our previous research found Aurora kinase A(AURKA) revives dormant LSCC to promote metastasis 3,5 .Therefore, illustrating speci c molecular mechanism of AURKA revives dormant LSCC to promote metastasiswasof great concern. The key moleculesmaybe capable to potential prognostic value and potential targets for clinical LSCC treatment.…”