The Suppression of <i>Aurora-A/STK15/BTAK</i> Expression Enhances Chemosensitivity to Docetaxel in Human Esophageal Squamous Cell Carcinoma

Tanaka, Eiji; Hashimoto, Yuichi; Ito, Takahiro; Kondo, Kan; Higashiyama, Motoshige; Tsunoda, Shigeru; Ortiz, Cristián; Sakai, Yoshiharu; Inazawa, Johji; Shimada, Yutaka

doi:10.1158/1078-0432.ccr-06-1192

Cited by 53 publications

(41 citation statements)

References 30 publications

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“…That has lead to test the proposal, in several laboratories, that experimental manipulation of the expression of genes coding for these proteins may be combined with MT-targeting drugs to improve their therapeutical efficacy. Well-documented instances include the genes encoding the mitotic protein kinases PLK1 (Spa¨nkuch et al, , 2007 and Aurora-A (Anand et al, 2003;Jiang et al, 2003;Hata et al, 2005;Tanaka et al, 2007), the MT-binding protein stathmin/ OP18, which has MT-destabilizing activity (Iancu et al, 2000(Iancu et al, , 2001Alli et al, 2002), and survivin, a member of the kinetochore-associated passenger proteins with MTstabilizing activity (Giodini et al, 2002;Carvalho et al, 2003;reviewed by Altieri, 2008). Relevant to the work reported here, survivin has been recently found to interact directly with Ran (Xia et al, 2008a, b).…”

Section: Discussionmentioning

confidence: 99%

RanBP1 downregulation sensitizes cancer cells to taxol in a caspase-3-dependent manner

et al. 2009

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Mitotic microtubule (MT)-targeting drugs are widely used to treat cancer. The GTPase Ran regulates multiple processes, including mitotic spindle assembly, spindle pole formation and MT dynamics; Ran activity is therefore essential to formation of a functional mitotic apparatus. The RanBP1 protein, which binds Ran and regulates its interaction with effectors, is overexpressed in many cancer types. Several observations indicate that RanBP1 contributes to regulate the function of the mitotic apparatus: RanBP1 inactivation yields hyperstable MTs and induces apoptosis during mitosis, reminiscent of the effects of the MT-stabilizing drug taxol. Here we have investigated the influence of RanBP1 on spontaneous and taxol-induced apoptosis in transformed cells. We report that RanBP1 downregulation by RNA interference activates apoptosis in several transformed cell lines regardless of their p53 status, but not in the caspase-3-defective MCF-7 breast cancer cell line. Furthermore, RanBP1-interfered cells show an increased apoptotic response to taxol compared to their counterpart with normal or high RanBP1 levels, and this response is caspase-3 dependent. These results indicate that RanBP1 can modulate the outcome of MT-targeting therapeutic protocols.

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Section: Discussionmentioning

confidence: 99%

RanBP1 downregulation sensitizes cancer cells to taxol in a caspase-3-dependent manner

et al. 2009

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“…HEEpiC cells were purchased from ScienCell Research Laboratories (Carlsbad, CA) and were cultured according to the manufacturer's instructions (14). The human ESCC cell lines KYSE-150, -170, -190, and -590 were maintained as described previously (14,15). KYSE-170 cells were transfected with oligoribonucleotides for miR-210 or negative control RNA (ncRNA) (Ambion, Austin, TX) using HiPerFect transfection reagent (Qiagen, Valencia, CA) according to the manufacturer's protocol for overexpression.…”

Section: Methodsmentioning

confidence: 99%

“…Assay of Cell Proliferation, Cell Cycle, and Cell Death-The WST-1 assay to measure cell proliferation and flow cytometric assays to analyze the cell cycle and cell death were performed with KYSE-170 cells at 48 h after transfection as described previously (15). Calculations for the analysis of the cell cycle were performed with ModFit software (BD Biosciences).…”

Section: Methodsmentioning

confidence: 99%

MicroRNA-210 Regulates Cancer Cell Proliferation through Targeting Fibroblast Growth Factor Receptor-like 1 (FGFRL1)

Tsuchiya

Fujiwara

Sato

et al. 2011

Journal of Biological Chemistry

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176

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The importance of microRNAs (miRNAs) in human malignancies has been well recognized. Here, we report that the expression of microRNA-210 (miR-210) is down-regulated in human esophageal squamous cell carcinoma and derived cell lines. Marked decreases in the level of miR-210 were observed especially in poorly differentiated carcinomas. We found that miR-210 inhibits cancer cell survival and proliferation by inducing cell death and cell cycle arrest in G 1 /G 0 and G 2 /M. Finally, we identified fibroblast growth factor receptor-like 1 (FGFRL1) as a target of miR-210 in esophageal squamous cell carcinoma and demonstrated that FGFRL1 accelerates cancer cell proliferation by preventing cell cycle arrest in G 1 /G 0 . Taken together, our findings show an important role for miR-210 as a tumor-suppressive microRNA with effects on cancer cell proliferation. MicroRNAs (miRNAs)2 are evolutionarily conserved small noncoding RNAs (20 -23 nucleotides) that bind to complementary sequences in the 3Ј-untranslated region (UTR) of target messenger RNAs (mRNAs) and regulate gene expression by the cleavage of target mRNAs and/or translational inhibition (1). Currently, Ͼ800 human miRNAs have been identified and registered in the miRNA database, miRBase (2). miRNAs play important roles in the differentiation of various cell types and in the initiation and progression of cancer, and it has been shown that the expression of some miRNAs is altered during cell differentiation and in malignancies (1, 3, 4).In a recent study, we identified microRNA-210 (miR-210) as one of the miRNAs that is markedly differentially expressed during the process of epithelial differentiation (3). It has been reported that miR-210 expression is down-regulated during epithelial-mesenchymal transition, the aberrant activation of which triggers cancer pathology (5). Carcinomas are derived from epithelial cells, and poor prognosis in patients with carcinoma is associated with the disruption of characteristics of differentiated epithelial cells, such as cell junctions and polarity (6 -8). Hence, given that the expression of miR-210 appears to be correlated well with epithelial differentiation, miR-210 might play a suppressive role in carcinomas. In support of this idea, allelic deletions at the miR-210 locus have been observed in 64% of cases of ovarian cancer (9), and ectopic expression of miR-210 represses tumor growth when human cancer cell lines are implanted into immunodeficient mice (10). However, the clinical roles of miR-210 in carcinomas and the mechanisms by which it represses tumor growth remain unknown.In this study, we investigated the functional role of miR-210 in the growth of carcinomas and the mechanism by which it acts using clinical samples as well as cell lines of esophageal squamous cell carcinoma (ESCC). ESCC is a highly aggressive malignancy with a 5-year survival rate of 10% worldwide. It has been used as a model to study the mechanisms of dysregulated epithelial differentiation and epithelial-mesenchymal transition in carcinomas (11, 12). E...

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“…(32) For esophageal squamous cell carcinoma cells, inhibition of Aurora-A suppressed tumor growth and sensitized the cells to docetaxel chemotherapy. (29) Moreover, our previous study showed that suppression of Aurora-A by VX-680 led to 46.0% tumor growth suppression, (33) suggesting Aurora-A might be a promising therapeutic molecular target for NPC and other types of HNSCC. However, the prognostic effect of Aurora-A has not been characterized in human NPC.…”

mentioning

confidence: 98%

“…(25) Indeed, Aurora-A overexpression has been found in a variety of malignancies, not only in solid tumors but also in leukemia, and predicted an inferior patient outcome. (25)(26)(27)(28)(29) Upregulation of Aurora-A mRNA, for example, was correlated with the occurrence of regional lymph node metastasis for HNSCC. (30,31) Conversely, inhibition of Aurora-A by its specific small molecule inhibitor VX-680 potently suppressed the laryngeal HepG2 cell AKT1/2 phosphorylation as well as migration capacity, and sensitized the cell to X-ray irradiation.…”

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confidence: 99%

Aurora‐A activation, correlated with hypoxia‐inducible factor‐1α, promotes radiochemoresistance and predicts poor outcome for nasopharyngeal carcinoma

et al. 2012

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Previously, we and others showed that hypoxia-inducible factor-1a (HIF-1a) and transcriptionally upregulated Aurora-A were required for disease progression in several tumors. Here, we address the clinicopathologic value of Aurora-A and HIF-1a in locally advanced nasopharyngeal carcinoma (NPC). Aurora-A and HIF-1a expression was semiquantitatively evaluated by immunohistochemistry staining in 144 cases from a randomized controlled trial. Of these patients, 69 received neoadjuvant chemotherapy plus concurrent chemoradiotherapy, and acted as the training set, and 75 cases treated with neoadjuvant chemotherapy plus radiotherapy were used as the testing set to validate the prognostic effect of Aurora-A and HIF-1a. We found that Aurora-A and HIF-1a were highly expressed in NPC, but were deficient in normal adjacent epithelia. In the testing set, Aurora-A overexpression predicted a shortened 5-year overall survival (59.1% vs 82.5%, P = 0.024), progressionfree survival (44.8% vs 79.8%, P = 0.004), and distant metastasisfree survival (43.0% vs 17.3%, P = 0.016). Multivariate regression analysis confirmed that Aurora-A was indeed an independent prognostic factor for death, recurrence, and distant metastasis both in the testing set and overall patients. Moreover, a positive correlation between Aurora-A and HIF-1a was detected (P = 0.037). Importantly, although HIF-1a did not show any prognostic effect for patient outcome, the subset with Aurora-A and HIF-1a co-overexpression had the poorest overall, progression-free, and distant metastasis-free survival (all P < 0.05). Our results confirmed that Aurora-A was an independent prognostic factor for NPC. Aurora-A combined with HIF-1a refined the risk definition of the patient subset, thus potentially directing locally advanced NPC patients for more selective therapy. (Cancer Sci 2012; 103: 1586-1594

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The Suppression of Aurora-A/STK15/BTAK Expression Enhances Chemosensitivity to Docetaxel in Human Esophageal Squamous Cell Carcinoma

Cited by 53 publications

References 30 publications

RanBP1 downregulation sensitizes cancer cells to taxol in a caspase-3-dependent manner

RanBP1 downregulation sensitizes cancer cells to taxol in a caspase-3-dependent manner

MicroRNA-210 Regulates Cancer Cell Proliferation through Targeting Fibroblast Growth Factor Receptor-like 1 (FGFRL1)

Aurora‐A activation, correlated with hypoxia‐inducible factor‐1α, promotes radiochemoresistance and predicts poor outcome for nasopharyngeal carcinoma

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