Tumor Heterogeneity in Breast Cancer

Turashvili, Gulisa; Brogi, Edi

doi:10.3389/fmed.2017.00227

Cited by 464 publications

(401 citation statements)

References 156 publications

Supporting

Mentioning

390

Contrasting

Unclassified

Order By: Relevance

“…Breast cancer is another example of inter-and intratumor heterogeneity, with different cell populations observed not only among different individuals, but sometimes also within the same tumor [184,185]. The critical importance of biomarkers in guiding treatment for breast cancer has long been established [186,187] and earlier discussed.…”

Section: Mirnas In Distinguishing Cancer Subtypesmentioning

confidence: 99%

miRNAs as Biomarkers in Disease: Latest Findings Regarding Their Role in Diagnosis and Prognosis

Condrat

Thompson

Barbu

et al. 2020

Cells

919

583

View full text Add to dashboard Cite

MicroRNAs (miRNAs) represent a class of small, non-coding RNAs with the main roles of regulating mRNA through its degradation and adjusting protein levels. In recent years, extraordinary progress has been made in terms of identifying the origin and exact functions of miRNA, focusing on their potential use in both the research and the clinical field. This review aims at improving the current understanding of these molecules and their applicability in the medical field. A thorough analysis of the literature consulting resources available in online databases such as NCBI, PubMed, Medline, ScienceDirect, and UpToDate was performed. There is promising evidence that in spite of the lack of standardized protocols regarding the use of miRNAs in current clinical practice, they constitute a reliable tool for future use. These molecules meet most of the required criteria for being an ideal biomarker, such as accessibility, high specificity, and sensitivity. Despite present limitations, miRNAs as biomarkers for various conditions remain an impressive research field. As current techniques evolve, we anticipate that miRNAs will become a routine approach in the development of personalized patient profiles, thus permitting more specific therapeutic interventions.Biogenesis of miRNA begins in the nucleus, where the transcription of its precursor, primary miRNA or pri-miRNA takes place under the influence of RNA polymerases II and III [11,12]. The resulting molecule is a hairpin-like structure, which contains a loop at one end [11]. This primordial mi-RNA precursor that is usually made up of hundreds of nucleotides is then processed consecutively by two RNase III enzymes [13][14][15]. The first enzyme to act upon the pri-miRNA, which still resides in the nucleus, is called Drosha or DCGR8, and turns it into a new hairpin-like structure of approximately 70 nucleotides, the Precursor-miRNA or pre-miRNA. The latter is then transported to the cytoplasm, with the help of Exportin-5, where it is cleaved again by the Ago2/Dicer complex leading to the short, mature miRNA double strands [16].Further on, one of the strands, usually known as the guide strand, will be integrated into the RNA-induced silencing complex (RISC), while the other one, known as the passenger strand, is going to be degraded, even though in some occasions it has been found to be also functional [17]. In most cases, the strand that contains the less stable 5 end or a uracil at the beginning is more likely to be selected as the guide strand [18][19][20]. In those situations, where the passenger strand is not degraded and both get incorporated into the miRISC complex, the mature miRNA in the guide strand will be the dominant one [21,22].The main role of miRNA in the human body is gene regulation [23] by mediating the degradation of mRNA and also by regulating transcription and translation through canonical and non-canonical mechanisms [4]. The canonical mechanism means that the miRISC complex containing the miRNA guide strand is exerting its action by binding to the targ...

show abstract

Section: Mirnas In Distinguishing Cancer Subtypesmentioning

confidence: 99%

miRNAs as Biomarkers in Disease: Latest Findings Regarding Their Role in Diagnosis and Prognosis

Condrat

Thompson

Barbu

et al. 2020

Cells

919

583

View full text Add to dashboard Cite

show abstract

“…In human breast cancer, intratumor heterogeneity can manifest in many ways, including on morphologic and genomic levels (Turashvili and Brogi, 2017). The importance of this heterogeneity is particularly notable when considering biomarker expression; for example, current recommendations report a positive finding if at least 1% of tumors cells are positive for the estrogen receptor (ER) (Hammond et al, 2010).…”

Section: Discussionmentioning

confidence: 99%

Targeting subtype-specific metabolic preferences in nucleotide biosynthesis inhibits tumor growth in a breast cancer model

Ogrodzinski¹,

Teoh²,

Lunt³

2020

Preprint

View full text Add to dashboard Cite

Investigating metabolic rewiring in cancer can lead to the discovery of new treatment strategies for breast cancer subtypes that currently lack targeted therapies. Using MMTV-Myc driven tumors to model breast cancer heterogeneity, we investigated metabolic differences between two histological subtypes, the epithelial-mesenchymal transition (EMT) and the papillary subtypes, using a combination of genomic and metabolomic techniques. We identified differences in nucleotide metabolism between EMT and papillary subtypes: EMT tumors preferentially use the nucleotide salvage pathway, while papillary tumors prefer de novo nucleotide biosynthesis. Using CRISPR/Cas9 gene editing and mass spectrometry-based methods, we determined that targeting the preferred pathway in each subtype resulted in greater metabolic impact than targeting the non-preferred pathway. We further show that knocking out the preferred nucleotide pathway in each subtype has a deleterious effect on in vivo tumor growth. In contrast, knocking out the non-preferred pathway has a lesser effect or results in increased tumor growth.

show abstract

“…This variability is an expected result considering the heterogeneous nature of BC subtypes. BC is a heterogeneous disease that differs greatly among different patients (inter-tumor heterogeneity) and even within the same tumor sample (intra-tumor heterogeneity) (43). Some of the samples in the TNBC group had either no or barely detectable GPD1 expression; thus, TNBC samples were suggested to be divided into two different groups, GPD1 + and GPD1 -.…”

Section: String Analysis Using Differentially Regulated Proteins Listmentioning

confidence: 99%

Comparative Proteome Analysis of Breast Cancer Tissues Highlights the Importance of Glycerol-3-phosphate Dehydrogenase 1 and Monoacylglycerol Lipase in Breast Cancer Metabolism

Yoneten

Kasap

Akpınar

et al. 2019

Cancer Genomics Proteomics

View full text Add to dashboard Cite

Background/Aim: Breast cancer (BC) incidence and mortality rates have been increasing due to the lack of appropriate diagnostic tools for early detection. Proteomicsbased studies may provide novel targets for early diagnosis and efficient treatment. The aim of this study was to investigate the global changes occurring in protein profiles in breast cancer tissues to discover potential diagnostic or prognostic biomarkers. Materials and Methods: BC tissues and their corresponding healthy counterparts were collected, subtyped, and subjected to comparative proteomics analyses using two-dimensional gel electrophoresis (2-DE) and twodimensional electrophoresis fluorescence difference gel (DIGE) coupled to matrix-assisted laser desorption/ ionisation-time of flight mass spectrometry (MALDI-TOF/TOF) to explore BC metabolism at the proteome level. Western blot analysis was used to verify changes occurring at the protein levels. Results: Bioinformatics analyses performed with differentially regulated proteins highlighted the changes occurring in triacylglyceride (TAG) metabolism, and directed our attention to TAG metabolism-associated proteins, namely glycerol-3-phosphate dehydrogenase 1 (GPD1) and monoacylglycerol lipase (MAGL). These proteins were downregulated in tumor groups in comparison to controls.Conclusion: GPD1 and MAGL might be promising tissuebased protein biomarkers with a predictive potential for BC.

show abstract

Tumor Heterogeneity in Breast Cancer

Cited by 464 publications

References 156 publications

miRNAs as Biomarkers in Disease: Latest Findings Regarding Their Role in Diagnosis and Prognosis

miRNAs as Biomarkers in Disease: Latest Findings Regarding Their Role in Diagnosis and Prognosis

Targeting subtype-specific metabolic preferences in nucleotide biosynthesis inhibits tumor growth in a breast cancer model

Comparative Proteome Analysis of Breast Cancer Tissues Highlights the Importance of Glycerol-3-phosphate Dehydrogenase 1 and Monoacylglycerol Lipase in Breast Cancer Metabolism

Contact Info

Product

Resources

About