Molecular Actions of Thyroid Hormone on Breast Cancer Cell Migration and Invasion via Cortactin/N-WASP

Uzair, Ivonne Denise; Grand, Jeremias Conte; Flamini, Marina Inés; Sanchez, Angel Matías

doi:10.3389/fendo.2019.00139

Cited by 20 publications

(22 citation statements)

References 41 publications

(57 reference statements)

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“…Lastly, the thyroid hormone pathway plays an important role as regulator of growth and metabolism. Nevertheless, dysfunction of the T3 hormone promotes cancer progression in mammary epithelial cells 86 .…”

Section: Discussionmentioning

confidence: 99%

OncoOmics approaches to reveal essential genes in breast cancer: a panoramic view from pathogenesis to precision medicine

López‐Cortés

Paz‐y‐Miño

Guerrero

et al. 2020

Sci Rep

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Breast cancer (Bc) is the leading cause of cancer-related death among women and the most commonly diagnosed cancer worldwide. Although in recent years large-scale efforts have focused on identifying new therapeutic targets, a better understanding of BC molecular processes is required. Here we focused on elucidating the molecular hallmarks of BC heterogeneity and the oncogenic mutations involved in precision medicine that remains poorly defined. To fill this gap, we established an OncoOmics strategy that consists of analyzing genomic alterations, signaling pathways, protein-protein interactome network, protein expression, dependency maps in cell lines and patient-derived xenografts in 230 previously prioritized genes to reveal essential genes in breast cancer. As results, the OncoOmics BC essential genes were rationally filtered to 140. mRNA up-regulation was the most prevalent genomic alteration. The most altered signaling pathways were associated with basal-like and Her2-enriched molecular subtypes . RAC1, AKT1, CCND1, PIK3CA, ERBB2, CDH1, MAPK14, TP53, MAPK1, SRC, RAC3, BCL2, CTNNB1, EGFR, CDK2, GRB2, MED1 and GATA3 were essential genes in at least three oncoomics approaches. Drugs with the highest amount of clinical trials in phases 3 and 4 were paclitaxel, docetaxel, trastuzumab, tamoxifen and doxorubicin. Lastly, we collected ~3,500 somatic and germline oncogenic variants associated with 50 essential genes, which in turn had therapeutic connectivity with 73 drugs. In conclusion, the OncoOmics strategy reveals essential genes capable of accelerating the development of targeted therapies for precision oncology.Breast cancer (BC) is a complex and heterogeneous disease characterized by an intricate interplay between different biological aspects such as ethnicity, genomic alterations, gene expression deregulation, hormone disruption, signaling pathway alterations, hypoxia, and environmental determinants 1,2 . Over the last years, prevention, treatment and survival strategies have evolved favorably; however, there are BC profiles that remain incurable 3 .

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Section: Discussionmentioning

confidence: 99%

OncoOmics approaches to reveal essential genes in breast cancer: a panoramic view from pathogenesis to precision medicine

López‐Cortés

Paz‐y‐Miño

Guerrero

et al. 2020

Sci Rep

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“…Lastly, the thyroid hormone signaling pathway is an important regulator of growth and metabolism. Nevertheless, deregulation of the T3 hormone levels could promote abnormal responsiveness of mammary epithelial cells developing BC 80 .…”

Section: Discussionmentioning

confidence: 99%

OncoOmics approaches to reveal essential genes in breast cancer: a panoramic view from pathogenesis to precision medicine

López‐Cortés

Paz‐y‐Miño

Guerrero

et al. 2019

Preprint

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SUMMARYBreast cancer (BC) is a heterogeneous disease where each OncoOmics approach needs to be fully understood as a part of a complex network. Therefore, the main objective of this study was to analyze genetic alterations, signaling pathways, protein-protein interaction networks, protein expression, dependency maps and enrichment maps in 230 previously prioritized genes by the Consensus Strategy, the Pan-Cancer Atlas, the Pharmacogenomics Knowledgebase and the Cancer Genome Interpreter, in order to reveal essential genes to accelerate the development of precision medicine in BC. The OncoOmics essential genes were rationally filtered to 144, 48 (33%) of which were hallmarks of cancer and 20 (14%) were significant in at least three OncoOmics approaches: RAC1, AKT1 CCND1, PIK3CA, ERBB2, CDH1, MAPK14, TP53, MAPK1, SRC, RAC3, PLCG1, GRB2, MED1, TOP2A, GATA3, BCL2, CTNNB1, EGFR and CDK2. According to the Open Targets Platform, there are 111 drugs that are currently being analyzed in 3151 clinical trials in 39 genes. Lastly, there are more than 800 clinical annotations associated with 94 genes in BC pharmacogenomics.

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“…Notably, this pathway can also stimulate cell proliferation and may have a role in different cancer types, such as T-cell lymphoma (TCL), colorectal cancer (CRC), and glioma [166][167][168]. By binding to αvβ3 in cancer cells, T4 activates transcription of a variety of genes that can stimulate cancer growth, such as genes with a function in signal transduction, angiogenesis, regulation of actin cytoskeleton, and epithelial-mesenchymal transition [168][169][170]. Interestingly, non-malignant cells express less αvβ3 than normal cells and, in addition, the conformation of the protein in normal cells seems to have a lower signal transduction activity [168].…”

Section: Non-genomic Th Actionmentioning

confidence: 99%

Genomic and Non-Genomic Mechanisms of Action of Thyroid Hormones and Their Catabolite 3,5-Diiodo-L-Thyronine in Mammals

Giammanco

Schiera

Liegro

2020

IJMS

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Since the realization that the cellular homologs of a gene found in the retrovirus that contributes to erythroblastosis in birds (v-erbA), i.e. the proto-oncogene c-erbA encodes the nuclear receptors for thyroid hormones (THs), most of the interest for THs focalized on their ability to control gene transcription. It was found, indeed, that, by regulating gene expression in many tissues, these hormones could mediate critical events both in development and in adult organisms. Among their effects, much attention was given to their ability to increase energy expenditure, and they were early proposed as anti-obesity drugs. However, their clinical use has been strongly challenged by the concomitant onset of toxic effects, especially on the heart. Notably, it has been clearly demonstrated that, besides their direct action on transcription (genomic effects), THs also have non-genomic effects, mediated by cell membrane and/or mitochondrial binding sites, and sometimes triggered by their endogenous catabolites. Among these latter molecules, 3,5-diiodo-L-thyronine (3,5-T2) has been attracting increasing interest because some of its metabolic effects are similar to those induced by T3, but it seems to be safer. The main target of 3,5-T2 appears to be the mitochondria, and it has been hypothesized that, by acting mainly on mitochondrial function and oxidative stress, 3,5-T2 might prevent and revert tissue damages and hepatic steatosis induced by a hyper-lipid diet, while concomitantly reducing the circulating levels of low density lipoproteins (LDL) and triglycerides. Besides a summary concerning general metabolism of THs, as well as their genomic and non-genomic effects, herein we will discuss resistance to THs and the possible mechanisms of action of 3,5-T2, also in relation to its possible clinical use as a drug.

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Molecular Actions of Thyroid Hormone on Breast Cancer Cell Migration and Invasion via Cortactin/N-WASP

Cited by 20 publications

References 41 publications

OncoOmics approaches to reveal essential genes in breast cancer: a panoramic view from pathogenesis to precision medicine

OncoOmics approaches to reveal essential genes in breast cancer: a panoramic view from pathogenesis to precision medicine

OncoOmics approaches to reveal essential genes in breast cancer: a panoramic view from pathogenesis to precision medicine

Genomic and Non-Genomic Mechanisms of Action of Thyroid Hormones and Their Catabolite 3,5-Diiodo-L-Thyronine in Mammals

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