An Integrative Analysis of the Tumorigenic Role of TAZ in Human Non–Small Cell Lung Cancer

Noguchi, Satoshi; Saito, Akira; Horie, Masafumi; Mikami, Yu; Suzuki, Hiroshi; Morishita, Yasuyuki; Ohshima, Mitsuhiro; Abiko, Yoshimitsu; Mattsson, Johanna Sofia Margareta; König, Helena; Lohr, Miriam; Edlund, Karolina; Botling, Johan; Micke, Patrick; Nagase, Takahide

doi:10.1158/1078-0432.ccr-13-3328

Cited by 77 publications

(102 citation statements)

References 51 publications

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“…Further experimentation with WWTR1 / TAZ knockdowns resulted in decreased lung tumor progression, while constitutively active WWTR1 / TAZ was found to be sufficient to drive lung tumor progression [40]. Additionally, higher TAZ expression levels in lung tumors have been shown to be predictive of worse prognoses [41, 42]. …”

Section: Discussionmentioning

confidence: 99%

Epigenome-wide association study of smoking and DNA methylation in non-small cell lung neoplasms

et al. 2016

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Tobacco smoke is a well-established lung cancer carcinogen. We hypothesize that epigenetic processes underlie carcinogenesis. The objective of this study is to examine the effects of smoke exposure on DNA methylation to search for novel susceptibility loci. We obtained epigenome-wide DNA methylation data from lung adenocarcinoma (LUAD) and lung squamous cell (LUSC) tissues in The Cancer Genome Atlas (TCGA). We performed a two-stage discovery (n = 326) and validation (n = 185) analysis to investigate the association of epigenetic DNA methylation level with cigarette smoking pack-years. We also externally validated our findings in an independent dataset. Linear model with least square estimator and spline regression were performed to examine the association between DNA methylation and smoking. We identified five CpG sites highly associated with pack-years of cigarette smoking. Smoking was negatively associated with methylation levels in cg25771041 (WWTR1, p = 3.6 × 10−9), cg16200496 (NFIX, p = 3.4 × 10−12), cg22515201 (PLA2G6, p = 1.0 × 10−9) and cg24823993 (NHP2L1, p = 5.1 × 10−8) and positively associated with the methylation level in cg11875268 (SMUG1, p = 4.3 × 10−8). The CpG-smoking association was stronger in LUSC than LUAD. Of the five loci, smoking explained the most variation in cg16200496 (R2 = 0.098 [both types] and 0.144 [LUSC]). We identified 5 novel CpG candidates that demonstrate differential methylation patterns associated with smoke exposure in lung neoplasms.

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Section: Discussionmentioning

confidence: 99%

Epigenome-wide association study of smoking and DNA methylation in non-small cell lung neoplasms

et al. 2016

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“…To investigate the mechanisms by which ABL kinases promote NSCLC metastasis, we carried out GSEA of the altered transcriptome induced by inactivation of the ABL kinases in PC9, PC9M, and H358 NSCLC cells. We found that pharmacological inhibition or knockdown of the ABL kinases markedly reduced the WNT/β-catenin ( Figure 5A and Supplemental Figure 6A) and TAZ ( Figure 5B and Supplemental Figure 6B) pathway signatures (18,27,28).…”

Section: Abl Kinases Promote Expression Of Genes Implicated In Nsclc mentioning

confidence: 93%

Inactivation of ABL kinases suppresses non–small cell lung cancer metastasis

Gu¹,

Rouse²,

Xu³

et al. 2016

JCI Insight

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“…The full texts of 37 articles were reviewed for more details and an additional 23 studies were excluded for insufficiency of survival data. Finally, 14 articles5,7–19 meeting the inclusion criteria were included. The study by Yuen et al included survival analyses for two different cohorts 12.…”

Section: Resultsmentioning

confidence: 99%

Prognostic significance of TAZ expression in various cancers: a meta-analysis

Feng¹,

Ren²,

Gou³

et al. 2016

OTT

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BackgroundThe overexpression of transcriptional coactivator with PDZ-binding motif (TAZ), a Hippo pathway effector, was detected in a variety of cancers. However, controversies remain in published studies on the prognostic value of TAZ expression in cancer. We performed a meta-analysis to demonstrate the prognostic significance of TAZ in overall survival (OS) and its association with clinicopathologic characteristics.MethodsA systematic literature search was performed by using PubMed, EMBASE, and Web of Science databases for eligible studies investigating the association between TAZ and survival. After extracting data, we used hazard ratio (HR), odds ratio (OR) and 95% confidence intervals (95% CIs) for association evaluation, I2 for heterogeneity across studies, and Egger’s test and Begg’s funnel plot for publication bias assessment.ResultsA total of 15 studies including 2,881 patients were analyzed. Pooled results showed that a high TAZ was significantly associated with poor OS (HR =1.82, 95% CI =1.58–2.11; I2=33%; P=0.11). Subgroup analysis indicated significant correlation between TAZ overexpression and OS in patients stratified by ethnicity, sample size, sample source, and staining location. Furthermore, TAZ overexpression was associated with worse OS in hepatocellular carcinoma (HR =2.26, 95% CI =1.43–3.57; P=0.49) and gastrointestinal cancers (HR =2.00, 95% CI =1.54–2.58; P=0.97), but not in non-small-cell lung cancer (HR =1.71, 95% CI =0.93–3.14; P=0.08). TAZ overexpression was also found to be significantly associated with some clinicopathologic characteristics, including TNM stage (OR =2.56, 95% CI =1.60–4.11; P=0.52), tumor differentiation (OR =3.08, 95% CI =1.25–7.63; P=0.01), and lymph node metastasis (OR =2.53, 95% CI =1.81–3.53; P=0.58).ConclusionTAZ overexpression is not only a predictive factor of poor prognosis but also associated with advanced TNM stage, poor tumor differentiation, and lymph node metastasis.

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An Integrative Analysis of the Tumorigenic Role of TAZ in Human Non–Small Cell Lung Cancer

Cited by 77 publications

References 51 publications

Epigenome-wide association study of smoking and DNA methylation in non-small cell lung neoplasms

Epigenome-wide association study of smoking and DNA methylation in non-small cell lung neoplasms

Inactivation of ABL kinases suppresses non–small cell lung cancer metastasis

Prognostic significance of TAZ expression in various cancers: a meta-analysis

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