scholarly journals p63 at the Crossroads between Stemness and Metastasis in Breast Cancer

2019 ◽  
Vol 20 (11) ◽  
pp. 2683 ◽  
Author(s):  
Veronica Gatti ◽  
Lucilla Bongiorno-Borbone ◽  
Claudia Fierro ◽  
Margherita Annicchiarico-Petruzzelli ◽  
Gerry Melino ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Progression ◽  
Breast Cancer Subtype ◽  
Physiological Role ◽  
The Past ◽  
Cancer Breast ◽  
Incidence And Mortality ◽  
Cancer Subtype ◽  
Screening Approaches

After lung cancer, breast cancer (BC) is the most frequent cause of cancer death among women, worldwide. Although advances in screening approaches and targeted therapeutic agents have decreased BC incidence and mortality, over the past five years, triple-negative breast cancer (TNBC) remains the breast cancer subtype that displays the worst prognosis, mainly due to the lack of clinically actionable targets. Genetic and molecular profiling has unveiled the high intrinsic heterogeneity of TNBC, with the basal-like molecular subtypes representing the most diffuse TNBC subtypes, characterized by the expression of basal epithelial markers, such as the transcription factor p63. In this review, we will provide a broad picture on the physiological role of p63, in maintaining the basal epithelial identity, as well as its involvement in breast cancer progression, emphasizing its relevance in tumor cell invasion and stemness.

scholarly journals The Complex Interaction between the Tumor Micro-Environment and Immune Checkpoints in Breast Cancer

Cancers ◽  
2019 ◽  
Vol 11 (8) ◽  
pp. 1205 ◽  
Author(s):  
Vanessa Barriga ◽  
Nyanbol Kuol ◽  
Kulmira Nurgali ◽  
Vasso Apostolopoulos
Keyword(s):  
Breast Cancer ◽  
Tumor Microenvironment ◽  
Cancer Progression ◽  
Molecular Subtypes ◽  
Breast Cancer Subtype ◽  
Complex Interaction ◽  
Immune Checkpoints ◽  
Expression Studies ◽  
Cancer Subtype ◽  
Insight Into

The progression of breast cancer and its association with clinical outcome and treatment remain largely unexplored. Accumulating data has highlighted the interaction between cells of the immune system and the tumor microenvironment in cancer progression, and although studies have identified multiple facets of cancer progression within the development of the tumor microenvironment (TME) and its constituents, there is lack of research into the associations between breast cancer subtype and staging. Current literature has provided insight into the cells and pathways associated with breast cancer progression through expression analysis. However, there is lack of co-expression studies between immune pathways and cells of the TME that form pro-tumorigenic relationships contributing to immune-evasion. We focus on the immune checkpoint and TME elements that influence cancer progression, particularly studies in molecular subtypes of breast cancer.

scholarly journals Transposon mutagenesis identifies genes that cooperate with mutant Pten in breast cancer progression

2016 ◽  
Vol 113 (48) ◽  
pp. E7749-E7758 ◽  
Author(s):  
Roberto Rangel ◽  
Song-Choon Lee ◽  
Kenneth Hon-Kim Ban ◽  
Liliana Guzman-Rojas ◽  
Michael B. Mann ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Progression ◽  
Epithelial To Mesenchymal Transition ◽  
Breast Cancer Subtype ◽  
Clinical Importance ◽  
Transposon Mutagenesis ◽  
Phosphatase And Tensin Homolog ◽  
Mesenchymal Transition ◽  
Tensin Homolog ◽  
Cancer Subtype

Triple-negative breast cancer (TNBC) has the worst prognosis of any breast cancer subtype. To better understand the genetic forces driving TNBC, we performed a transposon mutagenesis screen in a phosphatase and tensin homolog (Pten) mutant mice and identified 12 candidate trunk drivers and a much larger number of progression genes. Validation studies identified eight TNBC tumor suppressor genes, including the GATA-like transcriptional repressorTRPS1. Down-regulation ofTRPS1in TNBC cells promoted epithelial-to-mesenchymal transition (EMT) by deregulating multiple EMT pathway genes, in addition to increasing the expression ofSERPINE1andSERPINB2and the subsequent migration, invasion, and metastasis of tumor cells. Transposon mutagenesis has thus provided a better understanding of the genetic forces driving TNBC and discovered genes with potential clinical importance in TNBC.

scholarly journals The histone H2B ubiquitin ligase RNF40 is required for HER2-driven mammary tumorigenesis

2020 ◽  
Vol 11 (10) ◽  
Author(s):  
Florian Wegwitz ◽  
Evangelos Prokakis ◽  
Anastasija Pejkovska ◽  
Robyn Laura Kosinsky ◽  
Markus Glatzel ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Progression ◽  
Ubiquitin Ligase ◽  
Transcriptional Activation ◽  
Breast Cancer Subtype ◽  
Mammary Tumorigenesis ◽  
Human Tumor ◽  
Her2 Positive ◽  
Number Of Patients

Abstract The HER2-positive breast cancer subtype (HER2+-BC) displays a particularly aggressive behavior. Anti-HER2 therapies have significantly improved the survival of patients with HER2+-BC. However, a large number of patients become refractory to current targeted therapies, necessitating the development of new treatment strategies. Epigenetic regulators are commonly misregulated in cancer and represent attractive molecular therapeutic targets. Monoubiquitination of histone 2B (H2Bub1) by the heterodimeric ubiquitin ligase complex RNF20/RNF40 has been described to have tumor suppressor functions and loss of H2Bub1 has been associated with cancer progression. In this study, we utilized human tumor samples, cell culture models, and a mammary carcinoma mouse model with tissue-specific Rnf40 deletion and identified an unexpected tumor-supportive role of RNF40 in HER2+-BC. We demonstrate that RNF40-driven H2B monoubiquitination is essential for transcriptional activation of RHO/ROCK/LIMK pathway components and proper actin-cytoskeleton dynamics through a trans-histone crosstalk with histone 3 lysine 4 trimethylation (H3K4me3). Collectively, this work demonstrates a previously unknown essential role of RNF40 in HER2+-BC, revealing the H2B monoubiquitination axis as a possible tumor context-dependent therapeutic target in breast cancer.

scholarly journals RNF40-dependent epigenetic regulation of actin cytoskeletal dynamics is required for HER2-driven mammary tumorigenesis

2020 ◽  
Author(s):  
Florian Wegwitz ◽  
Evangelos Prokakis ◽  
Anastasija Pejkovska ◽  
Robyn Laura Kosinsky ◽  
Markus Glatzel ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Progression ◽  
Transcriptional Activation ◽  
Breast Cancer Subtype ◽  
Human Tumor ◽  
Actin Dynamics ◽  
Her2 Positive ◽  
Her2 Positive Breast Cancer ◽  
Positive Breast Cancer

AbstractThe HER2-driven breast cancer subtype displays a particularly aggressive behavior. Alterations of the epigenome are common in cancers and represent attractive novel molecular therapeutic targets. Monoubiquitination of histone 2B (H2Bub1) by its obligate heterodimeric E3 ubiquitin ligase complex RNF20/RNF40 has been described to have tumor suppressor functions and loss of H2Bub1 has been associated with cancer progression. In this study, we utilized human tumor samples, cell culture models, and a mammary carcinoma mouse model with tissue-specific Rnf40 deletion and identified an unexpected tumor-supportive role of RNF40 in HER2-positive breast cancer. We demonstrate that RNF40-driven H2B monoubiquitination is essential for transcriptional activation of RHO/ROCK/LIMK pathway components and proper actin cytoskeleton dynamics through a trans-histone crosstalk with histone 3 lysine 4 trimethylation (H3K4me3). Collectively, this work demonstrates a previously unknown essential role of RNF40 in HER2-positive breast cancer, revealing the RNF20/RNF40/H2Bub1 axis as a possible tumor context-dependent therapeutic target in breast cancer.Statement of significanceHER2-positive breast cancer patients frequently develop resistance to anti-HER2 therapies. Here we demonstrate that RNF20/RNF40-mediated H2B monoubiquitination supports the oncogenic properties of cancer cells of this subtype by regulating actin dynamics. The RNF20/RNF40/H2Bub1 axis may therefore represent an attractive drug target for novel therapies.

scholarly journals Prognostic Role of Interleukin-6, Interleukin-8, and Leptin Levels According to Breast Cancer Subtype

2013 ◽  
Vol 45 (3) ◽  
pp. 210-219 ◽  
Author(s):  
Young Ae Cho ◽  
Mi-Kyung Sung ◽  
Jee-Young Yeon ◽  
Jungsil Ro ◽  
Jeongseon Kim
Keyword(s):  
Breast Cancer ◽  
Interleukin 6 ◽  
Breast Cancer Subtype ◽  
Interleukin 8 ◽  
Prognostic Role ◽  
Cancer Subtype
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