scholarly journals Single cell transcriptomics reveals involution mimicry during the specification of the basal breast cancer subtype

2019 ◽  
Author(s):  
Fatima Valdes-Mora ◽  
Robert Salomon ◽  
Brian Gloss ◽  
Andrew MK. Law ◽  
Lesley Castillo ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Single Cell ◽  
Cancer Cells ◽  
Tumour Progression ◽  
Breast Cancer Subtype ◽  
Luminal Breast Cancer ◽  
Luminal Progenitor ◽  
Mesenchymal Transition ◽  
Basal Breast Cancer ◽  
Cancer Subtype

AbstractBoth luminal and basal breast cancer subtypes originate in the mammary luminal progenitor cell compartment. Basal breast cancer is associated with younger age, early relapse, and high mortality rate. Here we used unbiased droplet-based single-cell RNAseq to elucidate the cellular basis of tumour progression during the specification of the basal breast cancer subtype from the luminal progenitor population. Basal–like cancer cells resembled the alveolar lineage that is specified upon pregnancy and showed molecular features indicative of an interaction with the tumour microenvironment (TME) including epithelial-to-mesenchymal transition (EMT), hypoxia, lactation and involution. Involution signatures in luminal breast cancer tumours with alveolar lineage features were associated with worse prognosis and features of basal breast cancer. Our high-resolution molecular characterisation of the tumour ecosystem also revealed a highly interactive cell-cell network reminiscent of an involution process. This involution mimicry involves malignant education of cancer-associated fibroblasts and myeloid cell recruitment to support tissue remodelling and sustained inflammation. Our study shows how luminal breast cancer acquires an aberrant post-lactation developmental program that involves both cancer cells and cells from the TME, to shift molecular subtype and promote tumour progression, with potential to explain the increased risk and poor prognosis of breast cancer associated to childbirth.

scholarly journals Single-Cell Analysis Reveals a Preexisting Drug-Resistant Subpopulation in the Luminal Breast Cancer Subtype

2019 ◽  
Vol 79 (17) ◽  
pp. 4412-4425 ◽  
Author(s):  
Marta Prieto-Vila ◽  
Wataru Usuba ◽  
Ryou-u Takahashi ◽  
Iwao Shimomura ◽  
Hideo Sasaki ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Single Cell ◽  
Single Cell Analysis ◽  
Breast Cancer Subtype ◽  
Luminal Breast Cancer ◽  
Drug Resistant ◽  
Cell Analysis ◽  
Cancer Subtype

scholarly journals Single-cell transcriptomics reveals involution mimicry during the specification of the basal breast cancer subtype

Cell Reports ◽  
2021 ◽  
Vol 35 (2) ◽  
pp. 108945
Author(s):  
Fátima Valdés-Mora ◽  
Robert Salomon ◽  
Brian Stewart Gloss ◽  
Andrew Man Kit Law ◽  
Jeron Venhuizen ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Single Cell ◽  
Breast Cancer Subtype ◽  
Basal Breast Cancer ◽  
Cancer Subtype

scholarly journals Single Cell Transcriptomics Reveals Involution Mimicry During the Specification of the Basal Breast Cancer Subtype

2020 ◽  
Author(s):  
Fatima Valdes-Mora ◽  
Robert Salomon ◽  
Brian Gloss ◽  
Andrew MK Law ◽  
Lesley Castillo ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Single Cell ◽  
Breast Cancer Subtype ◽  
Basal Breast Cancer ◽  
Cancer Subtype

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.

Abstract A023: Investigating differential expression of microRNAs in the luminal breast cancer subtype

2013 ◽  
Author(s):  
Dylan A. Ehman ◽  
Dushanthi Pinnaduwage ◽  
Shelley B. Bull ◽  
Irene L. Andrulis
Keyword(s):  
Breast Cancer ◽  
Differential Expression ◽  
Breast Cancer Subtype ◽  
Luminal Breast Cancer ◽  
Cancer Subtype

scholarly journals Sumoylation Pathway Is Required to Maintain the Basal Breast Cancer Subtype

Cancer Cell ◽  
2014 ◽  
Vol 25 (6) ◽  
pp. 748-761 ◽  
Author(s):  
Maria V. Bogachek ◽  
Yizhen Chen ◽  
Mikhail V. Kulak ◽  
George W. Woodfield ◽  
Anthony R. Cyr ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Breast Cancer Subtype ◽  
Basal Breast Cancer ◽  
Cancer Subtype

scholarly journals Breast cancer as an example of tumour heterogeneity and tumour cell plasticity during malignant progression

2021 ◽  
Author(s):  
Fabiana Lüönd ◽  
Stefanie Tiede ◽  
Gerhard Christofori
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Tumour Cell ◽  
Current Knowledge ◽  
Tumour Progression ◽  
Malignant Tumour ◽  
Cell Plasticity ◽  
Tumour Heterogeneity ◽  
Extrinsic Factors ◽  
Mesenchymal Transition

AbstractHeterogeneity within a tumour increases its ability to adapt to constantly changing constraints, but adversely affects a patient’s prognosis, therapy response and clinical outcome. Intratumoural heterogeneity results from a combination of extrinsic factors from the tumour microenvironment and intrinsic parameters from the cancer cells themselves, including their genetic, epigenetic and transcriptomic traits, their ability to proliferate, migrate and invade, and their stemness and plasticity attributes. Cell plasticity constitutes the ability of cancer cells to rapidly reprogramme their gene expression repertoire, to change their behaviour and identities, and to adapt to microenvironmental cues. These features also directly contribute to tumour heterogeneity and are critical for malignant tumour progression. In this article, we use breast cancer as an example of the origins of tumour heterogeneity (in particular, the mutational spectrum and clonal evolution of progressing tumours) and of tumour cell plasticity (in particular, that shown by tumour cells undergoing epithelial-to-mesenchymal transition), as well as considering interclonal cooperativity and cell plasticity as sources of cancer cell heterogeneity. We review current knowledge on the functional contribution of cell plasticity and tumour heterogeneity to malignant tumour progression, metastasis formation and therapy resistance.

scholarly journals ROLE OF TRANSFORMING GROWTH FACTOR RECEPTOR B I TYPE (TGF-BRI) IN THE PROGRESSION OF THE LUMINAL BREAST CANCER SUBTYPE

2017 ◽  
Vol 16 (2) ◽  
pp. 27-35
Author(s):  
N. N. Babyshkina ◽  
S. V. Vtorushin ◽  
T. A. Dronova ◽  
N. V. Krakhmal ◽  
M. V. Zavyalova ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Growth Factor ◽  
Transforming Growth Factor ◽  
Breast Cancer Subtype ◽  
Growth Factor Receptor ◽  
Luminal Breast Cancer ◽  
Cancer Subtype ◽  
Transforming Growth Factor Receptor

scholarly journals β-Catenin haploinsufficiency promotes mammary tumorigenesis in an ErbB2-positive basal breast cancer model

2017 ◽  
Vol 114 (5) ◽  
pp. E707-E716 ◽  
Author(s):  
Tung Bui ◽  
Babette Schade ◽  
Robert D. Cardiff ◽  
Olulanu H. Aina ◽  
Virginie Sanguin-Gendreau ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Target Genes ◽  
Adherens Junctions ◽  
Tumor Formation ◽  
Luminal Breast Cancer ◽  
Mesenchymal Transition ◽  
Tumor Onset ◽  
Tyrosine Kinase 2 ◽  
Basal Breast Cancer ◽  
Positive Breast Cancer

Aberrant activation of β-catenin through its activity as a transcription factor has been observed in a large proportion of human malignancies. Despite the improved understanding of the β-catenin signaling pathway over the past three decades, attempts to develop therapies targeting β-catenin remain challenging, and none of these targeted therapies have advanced to the clinic. In this study, we show that part of the challenge in antagonizing β-catenin is caused by its dual functionality as a cell adhesion molecule and a signaling molecule. In a mouse model of basal ErbB2 receptor tyrosine kinase 2 (ErbB2)-positive breast cancer (ErbB2KI), which exhibits aberrant β-catenin nuclear signaling, β-catenin haploinsufficiency induced aggressive tumor formation and metastasis by promoting the disruption of adherens junctions, dedifferentiation, and an epithelial to mesenchymal transition (EMT) transcriptional program. In contrast to the accelerated tumor onset observed in the haploid-insufficient ErbB2 tumors, deletion of both β-catenin alleles in the ErbB2KImodel had only a minor impact on tumor onset that further correlated with the retention of normal adherens junctions. We further showed that retention of adherens junctional integrity was caused by the up-regulation of the closely related family member plakoglobin (γ-catenin) that maintained both adherens junctions and the activation of Wnt target genes. In contrast to the ErbB2KIbasal tumor model, modulation of β-catenin levels had no appreciable impact on tumor onset in an ErbB2-driven model of luminal breast cancer [murine mammary tumor virus promoter (MMTV-NIC)]. These observations argue that the balance of junctional and nuclear β-catenin activity has a profound impact on tumor progression in this basal model of ErbB2-positive breast cancer.

scholarly journals Analyzing mRNAsi-Related Genes Identifies Novel Prognostic Markers and Potential Drug Combination for Patients with Basal Breast Cancer

2021 ◽  
Vol 2021 ◽  
pp. 1-15
Author(s):  
Kai Huang ◽  
Yu Wu ◽  
YunQing Xie ◽  
LiYing Huang ◽  
Hong Liu
Keyword(s):  
Breast Cancer ◽  
Prognostic Factors ◽  
Prognostic Model ◽  
Drug Sensitivity ◽  
Learning Algorithm ◽  
Breast Cancer Subtype ◽  
Metabolic Reprogramming ◽  
Cancer Subtypes ◽  
Basal Breast Cancer ◽  
Cancer Subtype

Basal breast cancer subtype is the worst prognosis subtypes among all breast cancer subtypes. Recently, a new tumor stemness index-mRNAsi is found to be able to measure the degree of oncogenic differentiation of tissues. The mRNAsi involved in a variety of cancer processes is derived from the innovative application of one-class logistic regression (OCLR) machine learning algorithm to the whole genome expression of various stem cells and tumor cells. However, it is largely unknown about mRNAsi in basal breast cancer. Here, we find that basal breast cancer carries the highest mRNAsi among all four subtypes of breast cancer, especially 385 mRNAsi-related genes are positively related to the high mRNAsi value in basal breast cancer. This high mRNAsi is also closely related to active cell cycle, DNA replication, and metabolic reprogramming in basal breast cancer. Intriguingly, in the 385 genes, TRIM59, SEPT3, RAD51AP1, and EXO1 can act as independent protective prognostic factors, but CTSF and ABHD4B can serve as independent bad prognostic factors in patients with basal breast cancer. Remarkably, we establish a robust prognostic model containing the 6 mRNAsi-related genes that can effectively predict the survival rate of patients with the basal breast cancer subtype. Finally, the drug sensitivity analysis reveals that some drug combinations may be effectively against basal breast cancer via targeting the mRNAsi-related genes. Taken together, our study not only identifies novel prognostic biomarkers for basal breast cancers but also provides the drug sensitivity data by establishing an mRNAsi-related prognostic model.

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