| 1. |
- Monteiro, Fatima Liliana, et al.
(författare)
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A Systematic Review to Define the Multi-Faceted Role of Lysine Methyltransferase SETD7 in Cancer
- 2022
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Ingår i: Cancers. - : MDPI AG. - 2072-6694. ; 14:6, s. 1414-
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Tidskriftsartikel (refereegranskat)abstract
- Simple Summary The protein methyltransferase SETD7 is essential for epigenetic regulation through methylation of histone H3 and non-histone proteins, including cell cycle, apoptosis and metastasis regulators. This multi-faceted role of SETD7 is cell context-and tissue type-dependent, which makes it difficult to interpret results in the framework of the current literature and to advance research in the field. The aim of this systematic review is to provide an updated description of how SETD7 impacts cancer-related processes considering different cancer types in different cell contexts. In the first part of this systematic review, we characterise the literature and in the second part, we provide a critical assessment of the findings from different cancer types. In the last part of this work, we integrate the findings and summarise the main signalling networks regulated by SETD7 to identify outcomes conserved across studies and propose ways to advance research related to SETD7. Histone-lysine N-methyltransferase SETD7 regulates a variety of cancer-related processes, in a tissue-type and signalling context-dependent manner. To date, there is no consensus regarding SETD7 ' s biological functions, or potential for cancer diagnostics and therapeutics. In this work, we summarised the literature on SETD7 expression and function in cancer, to identify the contexts where SETD7 expression and targeting can lead to improvements in cancer diagnosis and therapy. The most studied cancers were found to be lung and osteosarcoma followed by colorectal and breast cancers. SETD7 mRNA and/or protein expression in human cancer tissue was evaluated using public databases and/or in-house cohorts, but its prognostic significance remains inconclusive. The most studied cancer-related processes regulated by SETD7 were cell proliferation, apoptosis, epithelial-mesenchymal transition, migration and invasion with special relevance to the pRb/E2F-1 pathway. SETD7 consistently prevented epithelial to mesenchymal transition in different cancer types, and inhibition of its function appears to be associated with improved response to DNA-damaging agents in most of the analysed studies. Stabilising mutations in SETD7 target proteins prevent their methylation or promote other competing post-translational modifications that can override the SETD7 effect. This indicates that a clear discrimination of these mutations and competing signalling pathways must be considered in future functional studies.
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| 2. |
- Monteiro, Fátima Liliana, et al.
(författare)
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Estrogen receptor beta expression and role in cancers
- 2024
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Ingår i: Journal of Steroid Biochemistry and Molecular Biology. - : Elsevier BV. - 0960-0760 .- 1879-1220. ; 242
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Tidskriftsartikel (refereegranskat)abstract
- Estrogen drives the growth of some cancers, such as breast cancer, via estrogen receptor alpha (ERα). Estrogen also activates ERβ, but whether ERβ is expressed and has a role in different cancers is debated. The use of nonspecific antibodies has contributed to the confusion, and this review delves into ERβ's controversial role in cancer and focuses on tumor expression that can be supported by non-antibody-dependent assays. We discuss its expression at the transcript level and focus on its potential role in lymphoma, granulosa cell tumors, testicular, and adrenal cancers, emphasizing recent findings and the complexities that necessitate further research.
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| 3. |
- Monteiro, Fatima Liliana, et al.
(författare)
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SETD7 Expression Is Associated with Breast Cancer Survival Outcomes for Specific Molecular Subtypes : A Systematic Analysis of Publicly Available Datasets
- 2022
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Ingår i: Cancers. - : MDPI AG. - 2072-6694. ; 14:24, s. 6029-
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Tidskriftsartikel (refereegranskat)abstract
- SETD7 is a lysine N-methyltransferase that targets many proteins important in breast cancer (BC). However, its role and clinical significance remain unclear. Here, we used online tools and multiple public datasets to explore the predictive potential of SETD7 expression (high or low quartile) considering BC subtype, grade, stage, and therapy. We also investigated overrepresented biological processes associated with its expression using TCGA-BRCA data. SETD7 expression was highest in the Her2 (ERBB2)-enriched molecular subtype and lowest in the basal-like subtype. For the basal-like subtype specifically, higher SETD7 was consistently correlated with worse recurrence-free survival (p < 0.009). High SETD7-expressing tumours further exhibited a higher rate of ERBB2 mutation (20% vs. 5%) along with a poorer response to anti-Her2 therapy. Overall, high SETD7-expressing tumours showed higher stromal and lower immune scores. This was specifically related to higher counts of cancer-associated fibroblasts and endothelial cells, but lower B and T cell signatures, especially in the luminal A subtype. Genes significantly associated with SETD7 expression were accordingly overrepresented in immune response processes, with distinct subtype characteristics. We conclude that the prognostic value of SETD7 depends on the BC subtype and that SETD7 may be further explored as a potential treatment-predictive marker for immune checkpoint inhibitors.
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| 4. |
- Monteiro, Fátima Liliana, et al.
(författare)
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The histone H2A isoform Hist2h2ac is a novel regulator of proliferation and epithelial-mesenchymal transition in mammary epithelial and in breast cancer cells.
- 2019
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Ingår i: Cancer Letters. - : Elsevier. - 0304-3835 .- 1872-7980. ; 396, s. 42-52
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Tidskriftsartikel (refereegranskat)abstract
- Proliferation and differentiation are controlled through chromatin remodelling. Therefore, there is an enormous biological significance and clinical value in understanding how specific signalling pathways are affected by histone replacement in the nucleosome. In this work, mass spectrometry was used to screen HC11 mammary epithelial cells for changes in histone levels throughout cell differentiation. The canonical histone isoform Histone H2A type 2-C (Hist2h2ac) was found only in undifferentiated/proliferating cells. Hist2h2ac mRNA was induced by EGF, specifically in the CD24+/CD29hi/DC44hi cell subpopulation. Hist2h2ac mRNA was increased by MEK(1/2) or PI3-K activation in HC11 and EpH4 mammary epithelial cells, and in MC4-L2 and T47-D breast cancer cells. Hist2h2ac silencing inhibited EGF-induced Zeb-1 expression and E-cadherin down-regulation, and this effect was reverted by Hist2h2ac re-expression. Notably, silencing of Hist2h2ac increased EGFR, ERBB2, and ERK(1/2) activation but did not allow EGF-induced proliferation. HIST2H2AC was expressed in all breast cancer molecular subtypes and found altered in 17% breast cancers, being 16.8% of the cases related to HIST2H2AC gene amplification and/or mRNA upregulation. In summary, this is the first study that identifies a canonical histone isoform -Hist2h2ac-downstream of the EGFR pathway, regulating oncogenic signalling and thereby contributing to deregulation of target genes.
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