Aurora-A signaling is activated in advanced stage of squamous cell carcinoma of head and neck cancer and requires osteopontin to stimulate invasive behavior

Chien, Chih Yen; Tsai, Hann-Huei; Su, Li; Chuang, Hui Ching; Shiu, Li Yen; Huang, Chao; Fang, Fu Min; Yu, Chun Chieh; Su, Hsuan; Chen, Chang Han

doi:10.18632/oncotarget.1896

Cited by 19 publications

(23 citation statements)

References 46 publications

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“…OPN has been studied as a potential therapeutic target in the regulation of cancer metastasis [ 39 – 41 ]. Activation of a CD44-dependent OPN/Aurora-A/ERK1/2 pathway has been reported, and OPN-activated Aurora-A has been proposed as a potential therapeutic target in head and neck squamous cell carcinoma [ 42 ]. Moreover, expression of OPN at histologically-negative surgical margins has been associated with higher recurrence of oral squamous cell carcinomas and, therefore, may be useful as a prognostic marker of recurrence [ 43 ].…”

Section: Introductionmentioning

confidence: 99%

Osteopontin (OPN/SPP1) isoforms collectively enhance tumor cell invasion and dissemination in esophageal adenocarcinoma

et al. 2015

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Esophageal adenocarcinoma (EAC) is often diagnosed at an advanced stage, thus understanding the molecular basis for EAC invasion and metastasis is critical. Here we report that SPP1/OPN was highly overexpressed in primary EACs and intracellularly localized to tumor cells. We further demonstrate that all known OPN isoforms (OPNa, b, c, 4 and 5) were frequently co-overexpressed in primary EACs. Distinct pro-invasion and dissemination phenotypes of isoform-specific OPNb and OPNc stable transfectants were observed. Expression of OPNb significantly enhanced cell migration and adhesion to laminin. In contrast, OPNc cells showed significantly decreased cell migration yet increased cell detachment. Enhanced invasion, both in vitro and in vivo, was observed for OPNb- but not OPNc-expressing cells. Inhibition of RGD integrins, one family of OPN receptors, attenuated OPNb cell migration, abrogated OPNb cell adhesion and significantly reduced OPNb cell clonogenic survival but did not affect OPNc phenotypes, indicating that OPNb but not OPNc acts through integrin-dependent signaling. Differential expression of vimentin, E-cadherin and β-catenin in OPN stable cells may account for the variation in cell adhesion and detachment between these isoforms. We conclude that while all OPN isoforms are frequently co-overexpressed in primary EACs, isoforms OPNb and OPNc enhance invasion and dissemination through collective yet distinct mechanisms.

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Section: Introductionmentioning

confidence: 99%

Osteopontin (OPN/SPP1) isoforms collectively enhance tumor cell invasion and dissemination in esophageal adenocarcinoma

et al. 2015

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“…Moreover, MER‐Erk1/2 and PI3K/Akt pathway could induced by FAK . Activation of osteopontin‐Aurora‐A‐Erk signaling is associated with progression, especially invasive capacity in head and neck squamous cell carcinoma . Furthermore, we found p‐AURKA upregulation could increase the level of p‐Erk1/2 and p‐AURKA downregulation could decrease the level of p‐Erk1/2.…”

Section: Discussionmentioning

confidence: 68%

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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“…Previous reports have indicated that either Aurora-A or FLJ10540 involves in multiple signaling pathways to promote cancer progression [ 12 , 13 , 15 , 17 , 24 , 25 ]. Intersection of these pathways elicited by either Aurora-A or FLJ10540, we found that these two molecules have shared common signal pathways for subsistence of tumor cells.…”

Section: Resultsmentioning

confidence: 99%

“…Our previous data indicated that FLJ10540 could form a complex with PI3K for promoting tumor growth in HCC [ 16 ]. Recently, we had demonstrated that Aurora-A was activated in advanced stage of squamous cell carcinoma of head and neck cancer [ 12 ]. In addition, FLJ10540 expression was correlated with aggressiveness of oral cavity squamous cell carcinoma [ 19 ].…”

Section: Discussionmentioning

confidence: 99%

Suppression of Aurora-A-FLJ10540 signaling axis prohibits the malignant state of head and neck cancer

Chen

Chang

et al. 2015

Mol Cancer

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BackgroundHead and neck cancer (HNC) is a highly invasive cancer. Aurora-A has been reported for a number of malignancies. However, the identity of downstream effectors responsible for its aggressive phenotype in HNC remains underinvestigated.MethodsThe mRNA and protein expression levels of Aurora-A and FLJ10540 were assessed in HNC specimens and cell lines using RT-qPCR, western blot, Oncomine, and microarray database analysis. The downstream molecular mechanisms of Aurora-A were confirmed by RT-qPCR, western blot, luciferase reporter, confocal microscopy analyses, immunoprecipitation, colony formation, cell viability, and xenograft model. Cellular functions in response to Aurora-A-modulated downstream targets such as FLJ10540 and MMPs were examined in vitro and in vivo, including cell growth, motility and chemosensitivity. Aurora-A/FLJ10540/MMPs expression was determined in cancer and adjacent normal tissues from HNC patients by immunohistochemistry approach.ResultsIn the current study, Aurora-A exhibited similar gene expression profiles with FLJ10540 by using accessibly public microarray and Oncomine database analysis, raising the possibility that these molecules might coordinately participate in cancer progression and metastasis of HNC. These two molecules connection were also examined in cell lines and tissues of HNC. Aurora-A overexpression could not only bind to the promoter of FLJ10540 to induce FLJ10540 expression, but also increase both mRNA and protein levels of MMP-7 and MMP-10 in HNC cells. Conversely, depletion of Aurora-A expression by using siRNA or Aurora-A kinase inhibitor, MLN8237, suppressed FLJ10540, MMP-7 and MMP-10 mRNA and protein expressions in vitro and in vivo. In addition, the FLJ10540-PI3K complex was destroyed by inhibition the Aurora-A kinase activity. Forced overexpression of FLJ10540 in Aurora-A-depleted or in MLN8237-treated HNC cells attenuated the effect on cytotoxicity to cisplatin. Elevated Aurora-A expression in HNC cells led to the characteristics of more aggressive malignancy, including enhanced chemoresistance and increased the abilities of proliferation, migration and invasion, which was required for FLJ10540/MMP-7 or FLJ10540/MMP-10 expressions. Finally, immunohistochemical analysis of human HNC specimens showed a significant positively correlation among Aurora-A, FLJ10540, MMP-7 and MMP-10 expressions.ConclusionTogether, our findings define a novel mechanism by which Aurora-A promotes cell malignancy, with potential implications for understanding the clinical action of Aurora-A.Electronic supplementary materialThe online version of this article (doi:10.1186/s12943-015-0348-7) contains supplementary material, which is available to authorized users.

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Aurora-A signaling is activated in advanced stage of squamous cell carcinoma of head and neck cancer and requires osteopontin to stimulate invasive behavior

Cited by 19 publications

References 46 publications

Osteopontin (OPN/SPP1) isoforms collectively enhance tumor cell invasion and dissemination in esophageal adenocarcinoma

Osteopontin (OPN/SPP1) isoforms collectively enhance tumor cell invasion and dissemination in esophageal adenocarcinoma

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

Suppression of Aurora-A-FLJ10540 signaling axis prohibits the malignant state of head and neck cancer

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