VGLL1 expression is associated with a triple-negative basal-like phenotype in breast cancer

Castilla, María Ángeles; López-García, María Ángeles; Atienza, M.; Rosa-Rosa, Juan Manuel; Díaz‐Martín, Juan; Pecero, María Luisa; Vieites, Begoña; Romero‐Pérez, Laura; Benítez, Javier; Calcabrini, Annarica; Palacios, José

doi:10.1530/erc-13-0485

Cited by 59 publications

(54 citation statements)

References 38 publications

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“…Therefore, the identification of specific biomarkers/molecular targets is imperative. In this regard, we have recently reported that Vgll1, a transcriptional cofactor with structural similarities to TAZ and YAP1, is mainly expressed in a subset of sporadic and BRCA1-associated TN/basal breast carcinomas (Castilla et al 2014). In a recent report by Bartucci et al (2014), TAZ IHC expression in a cohort of 99 tumors was not significantly correlated with receptor status, although the authors did observe an association between high tumor grade and Ki67 index, as we have observed in the present study.…”

Section: Discussioncontrasting

confidence: 50%

“…A series of 640 formalin-fixed paraffin-embedded (FFPE) human invasive breast carcinomas, including some cases from a previous study (Castilla et al 2014) and an independent tumor set of 15 metaplastic breast carcinomas (MBC), were obtained from the archives of the Department of Pathology of the Hospital Universitario Virgen del Rocío, Sevilla, Spain. The tumors had been diagnosed between 2007 and 2011, and the only selection criteria were the availability of pathological data and tissue for tissue microarray (TMA) construction.…”

Section: Human Tumorsmentioning

confidence: 99%

“…The real-time quantitative RT-PCR (qRT-PCR) for WWTR1 and YAP1 was performed with gene-specific fluorescent Taqman probes (Taqman Gene Expression Assays, Applied Biosystems), using MRPL19 as the endogenous control to normalize for variations in the quantity of the input cDNA. Details of qRT-PCR have been previously described (Castilla et al 2012(Castilla et al , 2014.…”

Section: Real-time Quantitative Rt-pcrmentioning

confidence: 99%

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Nuclear TAZ expression associates with the triple-negative phenotype in breast cancer

Díaz‐Martín¹,

López-García²,

Romero‐Pérez³

et al. 2015

Endocrine-Related Cancer

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The Hippo signaling pathway, a conserved regulator of organ size, has emerged as an important regulatory pathway in cancer. The final transducer effectors of this pathway in mammals are the oncoproteins TAZ and YAP1, which are transcriptional coactivators of target genes involved in cell proliferation and survival. TAZ has been previously reported to play a role in tumorigenesis in breast cancer, but detailed analyses of the different breast cancer phenotypes have not been conducted thus far. We analyzed TAZ expression by immunohistochemistry in a retrospective series of 640 invasive breast carcinomas, comprising estrogen/progesterone receptor-positive (ERC/PRC), HER2-positive, and triple-negative (TN) tumors. We found a strong association of TAZ nuclear expression with the TN phenotype (60.5% TAZ-positive, P!0.001), which was strengthened when stratified into the basal-like subtype (70.8% TAZ-positive, P!0.001). Moreover, 90% of metaplastic breast carcinomas with morphological epithelial-mesenchymal transition features were TAZ-positive. We also investigated whether amplification or differential DNA methylation of the TAZ-encoding locus could account for the observed enhanced TAZ protein expression in the TN/basal phenotype. Amplification of the TAZ locus was analyzed by fluorescence in situ hybridization in 30 TN tumors, and we found gene amplification in some cases (6.45%). DNA methylation analysis was performed using the Sequenom MassArray MALDI-TOF platform, and we observed similar low methylation levels both in TN (nZ25) and ERC/PRC (nZ26) tumors. These results were further confirmed using a panel of breast cancer cell lines and using the TCGA dataset. Finally, patients with strong TAZ expression showed poorer clinical outcomes with respect to both recurrence and overall survival.

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Section: Discussioncontrasting

confidence: 50%

Section: Human Tumorsmentioning

confidence: 99%

Section: Real-time Quantitative Rt-pcrmentioning

confidence: 99%

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Nuclear TAZ expression associates with the triple-negative phenotype in breast cancer

Díaz‐Martín¹,

López-García²,

Romero‐Pérez³

et al. 2015

Endocrine-Related Cancer

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“…The miR-934 was the most strongly up-regulated microRNA in triple-negative IDCs (61.5-fold increase with respect to ER+ breast carcinomas) 32. Although studies about hsa-miR-3196 are rare, it was found that miR-3196 was down-regulated in basal cell carcinoma compared with nonlesional skin 33, and was also down-regulated in PTC patients with non-(131) I-avid lung metastases versus (131)I-avid lung metastases 34.…”

Section: Discussionmentioning

confidence: 98%

MicroRNA Signature of Lung Adenocarcinoma with EGFR Exon 19 Deletion

Ju¹,

Han²,

Li³

et al. 2017

J. Cancer

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The findings of EGFR mutations and the development of targeted therapies have significantly improved the overall survival of lung cancer patients. Still, the prognosis remains poor, so we need to know more about the genetic alterations in lung cancer. MicroRNAs are dysregulated in lung cancer, and some of them can regulate EGFR. So it is very important to predict the candidate microRNAs that target mutated EGFR and to investigate the role of these candidate microRNAs in lung cancer. In this study, we investigated the difference of microRNAs expression between lung adenocarcinoma cell lines with EGFR exon 19 deletion (H1650 and PC9) and wild-type (H1299 and A549) using the Phalanx Human Whole Genome Microarray. Then the expression of individual microRNAs was validated by qRT-PCR assays. Moreover, we detected the microRNAs expression in plasma of lung adenocarcinoma patients with EGFR exon 19 deletion and wild-type. Lastly, we explored the function of the positive microRNA in EGFR tyrosine kinase inhibitors (EGFR-TKIs ) resistance using MTT and Annexin V-APC assays. The expression of 1,732 microRNAs was evaluated, and we found that microRNAs expression was different between these two groups. Hsa-miR-141-3p, hsa-miR-200c-3p, hsa-miR-203, hsa-miR-3182, hsa-miR-934 were up-regulated and hsa-miR-3196 was down-regulated in the EGFR exon 19 deletion group compared with wild-type group. The detection of circulating microRNAs showed that miR-3196 was down-regulated in lung adenocarcinoma patients with EGFR exon 19 deletion compared with wild-type. And then the MTT assay results showed that miR-3196 had no effect on the sensitivity of erlotinib. The results of apoptosis analysis showed that inhibition of miR-3196 and erlotinib induced more apoptosis in H1299 cells than erlotinib alone, and overexpressed miR-3196 and erlotinib induced less apoptosis in PC9 cells than erlotinib alone (P<0.05). It is suggested that microRNAs associate with EGFR exon 19 deletion and miR-3196 may be further explored as a potential predictor and targeted biomarker when it is difficult to get the tumors.

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“…Moreover, several other keratins (e.g., KRT14, KRT15) are included to construct the gene interaction network. VGLL1 (Vestigial-like 1) is a gene encoding a transcriptional co-activator modulating the Hippo pathway, which is known to be associated with a basal-like phenotype in breast cancer36. Participation of FZD9 in carcinogenesis has been reported in various cancers, indicating their potential roles in breast cancer, such as mTOR signaling pathway.…”

Section: Discussionmentioning

confidence: 99%

Exploring the intrinsic differences among breast tumor subtypes defined using immunohistochemistry markers based on the decision tree

Bai

Dai

2016

Sci Rep

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Exploring the intrinsic differences among breast cancer subtypes is of crucial importance for precise diagnosis and therapeutic decision-making in diseases of high heterogeneity. The subtypes defined with several layers of information are related but not consistent, especially using immunohistochemistry markers and gene expression profiling. Here, we explored the intrinsic differences among the subtypes defined by the estrogen receptor, progesterone receptor and human epidermal growth factor receptor 2 based on the decision tree. We identified 30 mRNAs and 7 miRNAs differentially expressed along the tree’s branches. The final signature panel contained 30 mRNAs, whose performance was validated using two public datasets based on 3 well-known classifiers. The network and pathway analysis were explored for feature genes, from which key molecules including FOXQ1 and SFRP1 were revealed to be densely connected with other molecules and participate in the validated metabolic pathways. Our study uncovered the differences among the four IHC-defined breast tumor subtypes at the mRNA and miRNA levels, presented a novel signature for breast tumor subtyping, and identified several key molecules potentially driving the heterogeneity of such tumors. The results help us further understand breast tumor heterogeneity, which could be availed in clinics.

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VGLL1 expression is associated with a triple-negative basal-like phenotype in breast cancer

Cited by 59 publications

References 38 publications

Nuclear TAZ expression associates with the triple-negative phenotype in breast cancer

Nuclear TAZ expression associates with the triple-negative phenotype in breast cancer

MicroRNA Signature of Lung Adenocarcinoma with EGFR Exon 19 Deletion

Exploring the intrinsic differences among breast tumor subtypes defined using immunohistochemistry markers based on the decision tree

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