Aurora kinase A revives dormant laryngeal squamous cell carcinoma cells via FAK/PI3K/Akt pathway activation

Yang, Liyun; He, Changyu; Chen, Xuehua; Su, Liping; Liu, Bingya; Zhang, Hao

doi:10.18632/oncotarget.10233

Cited by 24 publications

(27 citation statements)

References 52 publications

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“…In our previous study, we indicated that LSCC might activate FAK/PI3K/Akt pathway to promote metastasis . FAK was the molecule involved in proliferation, migration, and invasion .…”

Section: Discussionmentioning

confidence: 97%

“…Recently, dormant state reactivation, the phenomenon in which residual disease was existent, but asymptomatic, might be played a great role in the metastasis of multiple cancers, for instance breast, prostate, and lung . Moreover, AURKA might activate dormant state to promote the metastasis of LSCC . Wang stated that dormant cancer cells might contain high levels of drug resistant genes .…”

Section: Discussionmentioning

confidence: 99%

“…In our previous study, AURKA was overexpressed in LSCC and associated with regional lymph node metastasis and late clinical stage . Moreover, AURKA might activate dormant state to promote the metastasis of LSCC . Wang stated that dormant cancer cells might contain high levels of drug‐resistant genes .…”

Section: Introductionmentioning

confidence: 95%

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

et al. 2019

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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.

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“…In our previous study, we indicated that LSCC might activate FAK/PI3K/Akt pathway to promote metastasis . FAK was the molecule involved in proliferation, migration, and invasion .…”

Section: Discussionmentioning

confidence: 97%

Section: Discussionmentioning

confidence: 99%

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

et al. 2019

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“…Studies have shown that PTEN and AURKA share certain common signaling pathways in malignant tumors (26)(27)(28)(29)(30)(31). Therefore, the present study analyzed the expression of PTEN in MGc803 and SGc7901 cells.…”

Section: Resultsmentioning

confidence: 93%

Low expression of PTEN is essential for maintenance of a malignant state in human gastric adenocarcinoma via upregulation of p‑AURKA mediated by activation of AURKA

Song

Liu

et al. 2018

Int J Mol Med

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Gastric adenocarcinoma remains a life‑threatening disease, emphasizing the importance of gaining an improved understanding of signaling pathways involved in this disease, which can lead to the development of novel therapeutic methods targeting common molecular pathways shared across different types of gastric adenocarcinoma. The present study revealed phosphatase and tensin homolog deleted on chromosome 10 (PTEN) and aurora kinase A (AURKA) gene alterations, which were involved in changes in the phenotypes of gastric cancer cells, including increased proliferation by cell counting kit‑8 assay and invasion capacity by Transwell invasion assay, and predicted survival rates by KM Plotter database in gastric cancer. The present study investigated the association between PTEN and AURKA. Western blotting revealed that phosphorylated (p)-AURKA correlated with two target genes, PTEN and AURKA. The downregulation of PTEN by small interfering (si)RNA not only increased the expression of AURKA at the mRNA and protein levels by western blotting and by reverse transcription‑quantitative PCR, but also increased the expression of p‑AURKA by western blotting and immunofluorescence analysis. In addition, western blotting and reverse transcription‑quantitative PCR revealed that the downregulation of AURKA affected the expression level of PTEN. Furthermore, PTEN suppressed the malignant phenotypic changes of gastric adenocarcinoma cells by regulating the expression of AURKA inhibited by p‑AURKA, suggesting that p‑AURKA may be the key mediator of the PTEN‑associated activation of AURKA and may be key in maintaining the PTEN‑induced malignant state of gastric adenocarcinoma cells. This hypothesis was confirmed by western blotting, and changes were observed in the protein expression of p‑AURKA and AURKA under conditions in which cells were treated with either MLN8237 or si‑PTEN transfection only, or with si‑PTEN transfection and MLN8237. Knockdown of the expression of PTEN altered the expression of p‑AKT, p‑glycogen synthase kinase 3β and β‑catenin, which are genes that have been reported to be involved in the development of gastric adenocarcinoma. The present study confirmed that p‑AURKA is important in the development of gastric adenocarcinoma and revealed a novel functional link between PTEN, AURKA and p‑AURKA activation. The results also suggest a novel drug design strategy in targeting PTEN and AURKA for more specific gastric cancer cell death that spares normal cells.

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“…Polymorphisms in the AURKA gene have been shown to increase the risk of primary breast cancer (26). Studies have revealed that the increased expression of AURKA is associated with laryngeal, nasopharyngeal and breast cancer metastasis (27)(28)(29)(30). AURKA has been demonstrated to be accountable for the phosphorylation of Breast Cancer 1, Early Onset (BRCA1) (31).…”

Section: Discussionmentioning

confidence: 99%

Network analysis revealed aurora kinase dysregulation in five gynecological types of cancer

Sethi

Mishra

2017

Oncol Lett

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Abstract. Gene markers are crucial for cancer prognosis and treatment. Previous studies have placed greater emphasis on individual diagnostic genes, thereby ignoring systemic-level attributes across diseases. Female-specific cells namely, breast, endometrium, cervical, ovarian and vulvar cells are highly susceptible to cancer. To date, a limited number of molecular studies have been performed that evaluate common biological processes across gynecological types of cancer. Differentially expressed genes in breast, cervical, endometrial, vulvar and ovarian cancer were utilized to construct protein-protein interaction networks, and to identify a common module across the five cancer types. A single common module with 8 nodes and 26 edges was mined among the five cancer systems. In total, four hub genes were present across the five cancer gene sets. Genes in the common module were enriched for the common pathways and associated diseases. The aurora kinase pathway was revealed to be conserved across the five cancer types surveyed. The present study, therefore, revealed that the aurora kinase pathway has a crucial function in the pathogenesis of the five aforementioned gynecological types of cancer through cross-tumor conservation.

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Aurora kinase A revives dormant laryngeal squamous cell carcinoma cells via FAK/PI3K/Akt pathway activation

Cited by 24 publications

References 52 publications

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

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

Low expression of PTEN is essential for maintenance of a malignant state in human gastric adenocarcinoma via upregulation of p‑AURKA mediated by activation of AURKA

Network analysis revealed aurora kinase dysregulation in five gynecological types of cancer

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