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Article: A new view of the mammary epithelial hierarchy and its implications for breast cancer initiation and metastasis.

Anstine, Lindsey J / Keri, Ruth

Journal of cancer metastasis and treatment

2019 Volume 5

Abstract: The existence of mammary epithelial stem cell (MaSC) populations capable of mediating mammary gland development and homeostasis has been established for over a decade. A combination of lineage tracing and mammary gland transplantation studies has ... ...

Abstract	The existence of mammary epithelial stem cell (MaSC) populations capable of mediating mammary gland development and homeostasis has been established for over a decade. A combination of lineage tracing and mammary gland transplantation studies has affirmed that MaSCs and their downstream progenitors are organized in a hierarchal manner; however, these techniques have failed to illuminate the complete spectrum of epithelial intermediate populations or their spatial and temporal relationships. The advent of single cell sequencing technology has allowed for characterization of highly heterogeneous tissues at high resolution. In the last two years, the remarkable advances in single cell RNA sequencing (scRNA-seq) technologies have been leveraged to address the heterogeneity of the mammary epithelium. These studies have afforded fresh insights into the transcriptional differentiation hierarchy and its chronology. Importantly, these data have led to a major conceptual shift in which the rigid boundaries separating stem, progenitor, and differentiated epithelial populations have been deconstructed, resulting in a new more fluid and flexible model of epithelial differentiation. The emerging view of the mammary epithelial hierarchy has important implications for mammary development, carcinogenesis, and metastasis, providing novel insights into the underlying cellular states that may promote malignant phenotypes.
Language	English
Publishing date	2019-06-13
Publishing country	United States
Document type	Journal Article
ZDB-ID	2819994-7
ISSN	2394-4722
ISSN	2394-4722
DOI	10.20517/2394-4722.2019.24
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Article ; Online: Up to your NEK2 in CIN.

Seachrist, Darcie D / Anstine, Lindsey J / Keri, Ruth A

Oncotarget

2021 Volume 12, Issue 8, Page(s) 723–725

Language	English
Publishing date	2021-04-13
Publishing country	United States
Document type	Editorial
ZDB-ID	2560162-3
ISSN	1949-2553 ; 1949-2553
ISSN (online)	1949-2553
ISSN	1949-2553
DOI	10.18632/oncotarget.27918
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Article ; Online: Centrosome Aberrations as Drivers of Chromosomal Instability in Breast Cancer.

Piemonte, Katrina M / Anstine, Lindsey J / Keri, Ruth A

Endocrinology

2021 Volume 162, Issue 12

Abstract: Chromosomal instability (CIN), or the dynamic change in chromosome number and composition, has been observed in cancer for decades. Recently, this phenomenon has been implicated as facilitating the acquisition of cancer hallmarks and enabling the ... ...

Abstract	Chromosomal instability (CIN), or the dynamic change in chromosome number and composition, has been observed in cancer for decades. Recently, this phenomenon has been implicated as facilitating the acquisition of cancer hallmarks and enabling the formation of aggressive disease. Hence, CIN has the potential to serve as a therapeutic target for a wide range of cancers. CIN in cancer often occurs as a result of disrupting key regulators of mitotic fidelity and faithful chromosome segregation. As a consequence of their essential roles in mitosis, dysfunctional centrosomes can induce and maintain CIN. Centrosome defects are common in breast cancer, a heterogeneous disease characterized by high CIN. These defects include amplification, structural defects, and loss of primary cilium nucleation. Recent studies have begun to illuminate the ability of centrosome aberrations to instigate genomic flux in breast cancer cells and the tumor evolution associated with aggressive disease and poor patient outcomes. Here, we review the role of CIN in breast cancer, the processes by which centrosome defects contribute to CIN in this disease, and the emerging therapeutic approaches that are being developed to capitalize upon such aberrations.
MeSH term(s)	Animals ; Breast Neoplasms/genetics ; Breast Neoplasms/pathology ; Centrosome/metabolism ; Centrosome/pathology ; Centrosome/physiology ; Chromosomal Instability/genetics ; Female ; Genomic Instability/genetics ; Humans
Language	English
Publishing date	2021-10-04
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, U.S. Gov't, Non-P.H.S. ; Review
ZDB-ID	427856-2
ISSN	1945-7170 ; 0013-7227
ISSN (online)	1945-7170
ISSN	0013-7227
DOI	10.1210/endocr/bqab208
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Article: FOXA1: A Pioneer of Nuclear Receptor Action in Breast Cancer.

Seachrist, Darcie D / Anstine, Lindsey J / Keri, Ruth A

Cancers

2021 Volume 13, Issue 20

Abstract: The pioneering function of FOXA1 establishes estrogen-responsive transcriptomes in luminal breast cancer. Dysregulated FOXA1 chromatin occupancy through focal amplification, mutation, or cofactor recruitment modulates estrogen receptor (ER) ... ...

Abstract	The pioneering function of FOXA1 establishes estrogen-responsive transcriptomes in luminal breast cancer. Dysregulated FOXA1 chromatin occupancy through focal amplification, mutation, or cofactor recruitment modulates estrogen receptor (ER) transcriptional programs and drives endocrine-resistant disease. However, ER is not the sole nuclear receptor (NR) expressed in breast cancers, nor is it the only NR for which FOXA1 serves as a licensing factor. Receptors for androgens, glucocorticoids, and progesterone are also found in the majority of breast cancers, and their functions are also impacted by FOXA1. These NRs interface with ER transcriptional programs and, depending on their activation level, can reprogram FOXA1-ER cistromes. Thus, NR interplay contributes to endocrine therapy response and resistance and may provide a vulnerability for future therapeutic benefit in patients. Herein, we review what is known regarding FOXA1 regulation of NR function in breast cancer in the context of cell identity, endocrine resistance, and NR crosstalk in breast cancer progression and treatment.
Language	English
Publishing date	2021-10-17
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2527080-1
ISSN	2072-6694
ISSN	2072-6694
DOI	10.3390/cancers13205205
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Article ; Online: TGF-β/activin signaling promotes CDK7 inhibitor resistance in triple-negative breast cancer cells through upregulation of multidrug transporters.

Webb, Bryan M / Bryson, Benjamin L / Williams-Medina, Eduardo / Bobbitt, Jessica R / Seachrist, Darcie D / Anstine, Lindsey J / Keri, Ruth A

The Journal of biological chemistry

2021 Volume 297, Issue 4, Page(s) 101162

Abstract: Cyclin-dependent kinase 7 (CDK7) is a master regulatory kinase that drives cell cycle progression and stimulates expression of oncogenes in a myriad of cancers. Inhibitors of CDK7 (CDK7i) are currently in clinical trials; however, as with many cancer ... ...

Abstract	Cyclin-dependent kinase 7 (CDK7) is a master regulatory kinase that drives cell cycle progression and stimulates expression of oncogenes in a myriad of cancers. Inhibitors of CDK7 (CDK7i) are currently in clinical trials; however, as with many cancer therapies, patients will most likely experience recurrent disease due to acquired resistance. Identifying targets underlying CDK7i resistance will facilitate prospective development of new therapies that can circumvent such resistance. Here we utilized triple-negative breast cancer as a model to discern mechanisms of resistance as it has been previously shown to be highly responsive to CDK7 inhibitors. After generating cell lines with acquired resistance, high-throughput RNA sequencing revealed significant upregulation of genes associated with efflux pumps and transforming growth factor-beta (TGF-β) signaling pathways. Genetic silencing or pharmacological inhibition of ABCG2, an efflux pump associated with multidrug resistance, resensitized resistant cells to CDK7i, indicating a reliance on these transporters. Expression of activin A (INHBA), a member of the TGF-β family of ligands, was also induced, whereas its intrinsic inhibitor, follistatin (FST), was repressed. In resistant cells, increased phosphorylation of SMAD3, a downstream mediator, confirmed an increase in activin signaling, and phosphorylated SMAD3 directly bound the ABCG2 promoter regulatory region. Finally, pharmacological inhibition of TGF-β/activin receptors or genetic silencing of SMAD4, a transcriptional partner of SMAD3, reversed the upregulation of ABCG2 in resistant cells and phenocopied ABCG2 inhibition. This study reveals that inhibiting the TGF-β/Activin-ABCG2 pathway is a potential avenue for preventing or overcoming resistance to CDK7 inhibitors.
MeSH term(s)	ATP Binding Cassette Transporter, Subfamily G, Member 2/biosynthesis ; ATP Binding Cassette Transporter, Subfamily G, Member 2/genetics ; Cell Line, Tumor ; Cyclin-Dependent Kinases/antagonists & inhibitors ; Cyclin-Dependent Kinases/genetics ; Cyclin-Dependent Kinases/metabolism ; Drug Resistance, Neoplasm/drug effects ; Drug Resistance, Neoplasm/genetics ; Female ; Gene Expression Regulation, Neoplastic/drug effects ; Humans ; Inhibin-beta Subunits/genetics ; Inhibin-beta Subunits/metabolism ; Neoplasm Proteins/biosynthesis ; Neoplasm Proteins/genetics ; Protein Kinase Inhibitors/pharmacology ; Signal Transduction/drug effects ; Signal Transduction/genetics ; Transforming Growth Factor beta/genetics ; Transforming Growth Factor beta/metabolism ; Triple Negative Breast Neoplasms/drug therapy ; Triple Negative Breast Neoplasms/genetics ; Triple Negative Breast Neoplasms/metabolism ; Triple Negative Breast Neoplasms/pathology ; Up-Regulation/drug effects
Chemical Substances	ABCG2 protein, human ; ATP Binding Cassette Transporter, Subfamily G, Member 2 ; Neoplasm Proteins ; Protein Kinase Inhibitors ; Transforming Growth Factor beta ; inhibin beta A subunit ; Inhibin-beta Subunits (93443-12-0) ; Cyclin-Dependent Kinases (EC 2.7.11.22) ; cyclin-dependent kinase-activating kinase (EC 2.7.11.22)
Language	English
Publishing date	2021-09-02
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, U.S. Gov't, Non-P.H.S.
ZDB-ID	2997-x
ISSN	1083-351X ; 0021-9258
ISSN (online)	1083-351X
ISSN	0021-9258
DOI	10.1016/j.jbc.2021.101162
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Article ; Online: TLE3 Sustains Luminal Breast Cancer Lineage Fidelity to Suppress Metastasis.

Anstine, Lindsey J / Majmudar, Parth R / Aponte, Amy / Singh, Salendra / Zhao, Ran / Weber-Bonk, Kristen L / Abdul-Karim, Fadi W / Valentine, Mitchell / Seachrist, Darcie D / Grennel-Nickelson, Katelyn E / Cuellar-Vite, Leslie / Sizemore, Gina M / Sizemore, Steven T / Webb, Bryan M / Thompson, Cheryl L / Keri, Ruth A

Cancer research

2023 Volume 83, Issue 7, Page(s) 997–1015

Abstract: Breast cancer subtypes and their phenotypes parallel different stages of the mammary epithelial cell developmental hierarchy. Discovering mechanisms that control lineage identity could provide novel avenues for mitigating disease progression. Here we ... ...

Abstract	Breast cancer subtypes and their phenotypes parallel different stages of the mammary epithelial cell developmental hierarchy. Discovering mechanisms that control lineage identity could provide novel avenues for mitigating disease progression. Here we report that the transcriptional corepressor TLE3 is a guardian of luminal cell fate in breast cancer and operates independently of the estrogen receptor. In luminal breast cancer, TLE3 actively repressed the gene-expression signature associated with highly aggressive basal-like breast cancers (BLBC). Moreover, maintenance of the luminal lineage depended on the appropriate localization of TLE3 to its transcriptional targets, a process mediated by interactions with FOXA1. By repressing genes that drive BLBC phenotypes, including SOX9 and TGFβ2, TLE3 prevented the acquisition of a hybrid epithelial-mesenchymal state and reduced metastatic capacity and aggressive cellular behaviors. These results establish TLE3 as an essential transcriptional repressor that sustains the more differentiated and less metastatic nature of luminal breast cancers. Approaches to induce TLE3 expression could promote the acquisition of less aggressive, more treatable disease states to extend patient survival. Significance: Transcriptional corepressor TLE3 actively suppresses SOX9 and TGFβ transcriptional programs to sustain the luminal lineage identity of breast cancer cells and to inhibit metastatic progression.
MeSH term(s)	Cell Differentiation ; Co-Repressor Proteins/genetics ; Neoplasms ; Receptors, Estrogen/metabolism ; Transcription Factors ; Transforming Growth Factor beta ; Breast Neoplasms/metabolism ; Humans
Chemical Substances	Co-Repressor Proteins ; Receptors, Estrogen ; Transcription Factors ; Transforming Growth Factor beta
Language	English
Publishing date	2023-01-23
Publishing country	United States
Document type	Journal Article ; Research Support, U.S. Gov't, Non-P.H.S. ; Research Support, N.I.H., Extramural
ZDB-ID	1432-1
ISSN	1538-7445 ; 0008-5472
ISSN (online)	1538-7445
ISSN	0008-5472
DOI	10.1158/0008-5472.CAN-22-3133
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Article ; Online: Contribution of Extra-Cardiac Cells in Murine Heart Valves is Age-Dependent.

Anstine, Lindsey J / Horne, Tori E / Horwitz, Edwin M / Lincoln, Joy

Journal of the American Heart Association

2017 Volume 6, Issue 10

Abstract: Background: Heart valves are dynamic structures that open and close over 100 000 times a day to maintain unidirectional blood flow during the cardiac cycle. Function is largely achieved by highly organized layers of extracellular matrix that provide the ...

Abstract	Background: Heart valves are dynamic structures that open and close over 100 000 times a day to maintain unidirectional blood flow during the cardiac cycle. Function is largely achieved by highly organized layers of extracellular matrix that provide the necessary biomechanical properties. Homeostasis of valve extracellular matrix is mediated by valve endothelial and interstitial cell populations, and although the embryonic origins of these cells are known, it is not clear how they are maintained after birth. The goal of this study is to examine the contribution of extracardiac cells to the aortic valve structure with aging using lineage tracing and bone marrow transplantation approaches. Methods and results: Immunohistochemistry and fate mapping studies using Conclusions: Findings from this study demonstrate that the percentage of CD45-positive extracardiac cells reside within endothelial and interstitial regions of heart valve structures increases with age. In addition, bone transplantation studies show that engraftment is dependent on the age of the donor and age of the tissue environment of the recipient. These studies create a foundation for further work defining the role of extracardiac cells in homeostatic and diseased heart valves.
MeSH term(s)	Age Factors ; Aging ; Animals ; Aortic Valve/cytology ; Aortic Valve/metabolism ; Biomarkers/metabolism ; Bone Marrow Transplantation ; CD11b Antigen/metabolism ; Cell Differentiation ; Cell Lineage ; Cell Survival ; Endothelial Cells/metabolism ; Endothelial Cells/physiology ; Green Fluorescent Proteins/biosynthesis ; Green Fluorescent Proteins/genetics ; Hematopoietic Stem Cells/metabolism ; Hematopoietic Stem Cells/physiology ; Integrases/genetics ; Leukocyte Common Antigens/biosynthesis ; Leukocyte Common Antigens/genetics ; Mice, Inbred C57BL ; Mice, Transgenic ; Phenotype ; Platelet Endothelial Cell Adhesion Molecule-1/metabolism ; Stem Cell Niche ; Vimentin/metabolism
Chemical Substances	Biomarkers ; CD11b Antigen ; Platelet Endothelial Cell Adhesion Molecule-1 ; Vimentin ; enhanced green fluorescent protein ; Green Fluorescent Proteins (147336-22-9) ; Cre recombinase (EC 2.7.7.-) ; Integrases (EC 2.7.7.-) ; Leukocyte Common Antigens (EC 3.1.3.48) ; PTPRC protein, human (EC 3.1.3.48)
Language	English
Publishing date	2017-10-20
Publishing country	England
Document type	Comparative Study ; Journal Article
ZDB-ID	2653953-6
ISSN	2047-9980 ; 2047-9980
ISSN (online)	2047-9980
ISSN	2047-9980
DOI	10.1161/JAHA.117.007097
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Article ; Online: Growth and maturation of heart valves leads to changes in endothelial cell distribution, impaired function, decreased metabolism and reduced cell proliferation.

Anstine, Lindsey J / Bobba, Chris / Ghadiali, Samir / Lincoln, Joy

Journal of molecular and cellular cardiology

2016 Volume 100, Page(s) 72–82

Abstract: Risk factors of heart valve disease are well defined and prolonged exposure throughout life leads to degeneration and dysfunction in up to 33% of the population. While aortic valve replacement remains the most common need for cardiovascular surgery ... ...

Abstract	Risk factors of heart valve disease are well defined and prolonged exposure throughout life leads to degeneration and dysfunction in up to 33% of the population. While aortic valve replacement remains the most common need for cardiovascular surgery particularly in those aged over 65, the underlying mechanisms of progressive deterioration are unknown. In other cardiovascular systems, a decline in endothelial cell integrity and function play a major role in promoting pathological changes, and while similar mechanisms have been speculated in the valves, studies to support this are lacking. The goal of this study was to examine age-related changes in valve endothelial cell (VEC) distribution, morphology, function and transcriptomes during critical stages of valve development (embryonic), growth (postnatal (PN)), maintenance (young adult) and aging (aging adult). Using a combination of in vivo mouse, and in vitro porcine assays we show that VEC function including, nitric oxide bioavailability, metabolism, endothelial-to-mesenchymal potential, membrane self-repair and proliferation decline with age. In addition, density of VEC distribution along the endothelium decreases and this is associated with changes in morphology, decreased cell-cell interactions, and increased permeability. These changes are supported by RNA-seq analysis showing that focal adhesion-, cell cycle-, and oxidative phosphorylation-associated biological processes are negatively impacted by aging. Furthermore, by performing high-throughput analysis we are able to report the differential and common transcriptomes of VECs at each time point that can provide insights into the mechanisms underlying age-related dysfunction. These studies suggest that maturation of heart valves over time is a multifactorial process and this study has identified several key parameters that may contribute to impairment of the valve to maintain critical structure-function relationships; leading to degeneration and disease.
MeSH term(s)	Aging ; Animals ; Cell Communication ; Cell Count ; Cell Proliferation ; Cells, Cultured ; Cellular Senescence/genetics ; Cluster Analysis ; Endothelial Cells/metabolism ; Endothelial Cells/ultrastructure ; Gene Expression Profiling ; Heart Valves/metabolism ; Heart Valves/pathology ; Heart Valves/ultrastructure ; Humans ; Mice ; Mice, Transgenic ; Nitric Oxide/metabolism ; Reactive Oxygen Species/metabolism ; Transcriptome
Chemical Substances	Reactive Oxygen Species ; Nitric Oxide (31C4KY9ESH)
Language	English
Publishing date	2016-11
Publishing country	England
Document type	Journal Article
ZDB-ID	80157-4
ISSN	1095-8584 ; 0022-2828
ISSN (online)	1095-8584
ISSN	0022-2828
DOI	10.1016/j.yjmcc.2016.10.006
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Article ; Online: Macrophage Transitions in Heart Valve Development and Myxomatous Valve Disease.

Hulin, Alexia / Anstine, Lindsey J / Kim, Andrew J / Potter, Sarah J / DeFalco, Tony / Lincoln, Joy / Yutzey, Katherine E

Arteriosclerosis, thrombosis, and vascular biology

2018 Volume 38, Issue 3, Page(s) 636–644

Abstract: Objective: Hematopoietic-derived cells have been reported in heart valves but remain poorly characterized. Interestingly, recent studies reveal infiltration of leukocytes and increased macrophages in human myxomatous mitral valves. Nevertheless, timing ... ...

Abstract	Objective: Hematopoietic-derived cells have been reported in heart valves but remain poorly characterized. Interestingly, recent studies reveal infiltration of leukocytes and increased macrophages in human myxomatous mitral valves. Nevertheless, timing and contribution of macrophages in normal valves and myxomatous valve disease are still unknown. The objective is to characterize leukocytes during postnatal heart valve maturation and identify macrophage subsets in myxomatous valve disease. Approach and results: Leukocytes are detected in heart valves after birth, and their numbers increase during postnatal valve development. Flow cytometry and immunostaining analysis indicate that almost all valve leukocytes are myeloid cells, consisting of at least 2 differentially localized macrophage subsets and dendritic cells. Beginning a week after birth, increased numbers of CCR2+ (C-C chemokine receptor type 2) macrophages are present, consistent with infiltrating populations of monocytes, and macrophages are localized in regions of biomechanical stress in the valve leaflets. Valve leukocytes maintain expression of CD (cluster of differentiation) 45 and do not contribute to significant numbers of endothelial or interstitial cells. Macrophage lineages were examined in aortic and mitral valves of Conclusions: Our study demonstrates the heterogeneity of myeloid cells in heart valves and highlights an alteration of macrophage subpopulations, notably an increased presence of infiltrating CCR2+ monocytes and CD206+ macrophages, in myxomatous valve disease.
MeSH term(s)	Age Factors ; Aged ; Animals ; Axin Protein/genetics ; Axin Protein/metabolism ; CX3C Chemokine Receptor 1/genetics ; CX3C Chemokine Receptor 1/metabolism ; Cell Lineage ; Dendritic Cells/metabolism ; Dendritic Cells/pathology ; Disease Models, Animal ; Extracellular Matrix/metabolism ; Extracellular Matrix/pathology ; Female ; Gene Expression Regulation, Developmental ; Genes, Reporter ; Heart Valve Diseases/genetics ; Heart Valve Diseases/metabolism ; Heart Valve Diseases/pathology ; Heart Valves/metabolism ; Heart Valves/pathology ; Humans ; Hyaluronic Acid/metabolism ; Lectins, C-Type/metabolism ; Leukocytes/metabolism ; Leukocytes/pathology ; Luminescent Proteins/genetics ; Luminescent Proteins/metabolism ; Macrophages/metabolism ; Macrophages/pathology ; Male ; Mannose-Binding Lectins/metabolism ; Mice, 129 Strain ; Mice, Inbred C57BL ; Mice, Knockout ; Mice, Transgenic ; Middle Aged ; Mutation ; Phenotype ; Receptors, CCR2/metabolism ; Receptors, Cell Surface/metabolism
Chemical Substances	Axin Protein ; Axin2 protein, mouse ; CX3C Chemokine Receptor 1 ; Ccr2 protein, mouse ; Cx3cr1 protein, mouse ; Lectins, C-Type ; Luminescent Proteins ; Mannose-Binding Lectins ; Receptors, CCR2 ; Receptors, Cell Surface ; mannose receptor ; Hyaluronic Acid (9004-61-9)
Language	English
Publishing date	2018-01-18
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	1221433-4
ISSN	1524-4636 ; 1079-5642
ISSN (online)	1524-4636
ISSN	1079-5642
DOI	10.1161/ATVBAHA.117.310667
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Article ; Online: LIN9 and NEK2 Are Core Regulators of Mitotic Fidelity That Can Be Therapeutically Targeted to Overcome Taxane Resistance.

Roberts, Melyssa S / Sahni, Jennifer M / Schrock, Morgan S / Piemonte, Katrina M / Weber-Bonk, Kristen L / Seachrist, Darcie D / Avril, Stefanie / Anstine, Lindsey J / Singh, Salendra / Sizemore, Steven T / Varadan, Vinay / Summers, Matthew K / Keri, Ruth A

Cancer research

2020 Volume 80, Issue 8, Page(s) 1693–1706

Abstract: A significant therapeutic challenge for patients with cancer is resistance to chemotherapies such as taxanes. Overexpression of LIN9, a transcriptional regulator of cell-cycle progression, occurs in 65% of patients with triple-negative breast cancer ( ... ...

Abstract	A significant therapeutic challenge for patients with cancer is resistance to chemotherapies such as taxanes. Overexpression of LIN9, a transcriptional regulator of cell-cycle progression, occurs in 65% of patients with triple-negative breast cancer (TNBC), a disease commonly treated with these drugs. Here, we report that LIN9 is further elevated with acquisition of taxane resistance. Inhibiting LIN9 genetically or by suppressing its expression with a global BET inhibitor restored taxane sensitivity by inducing mitotic progression errors and apoptosis. While sustained LIN9 is necessary to maintain taxane resistance, there are no inhibitors that directly repress its function. Hence, we sought to discover a druggable downstream transcriptional target of LIN9. Using a computational approach, we identified NIMA-related kinase 2 (NEK2), a regulator of centrosome separation that is also elevated in taxane-resistant cells. High expression of
MeSH term(s)	Antineoplastic Agents/administration & dosage ; Antineoplastic Agents/pharmacology ; Apoptosis ; Cell Line, Tumor ; Cellular Senescence ; Centrosome/enzymology ; Drug Resistance, Neoplasm/drug effects ; Female ; Gene Expression Regulation, Neoplastic ; Gene Silencing ; Heterografts ; Humans ; Mitosis/drug effects ; Mitosis/genetics ; NIMA-Related Kinases/antagonists & inhibitors ; NIMA-Related Kinases/metabolism ; Neoplasm Proteins/antagonists & inhibitors ; Neoplasm Proteins/metabolism ; Nuclear Proteins/antagonists & inhibitors ; Nuclear Proteins/metabolism ; Paclitaxel/administration & dosage ; Paclitaxel/pharmacology ; Survival Rate ; Taxoids/administration & dosage ; Taxoids/pharmacology ; Triple Negative Breast Neoplasms/drug therapy ; Triple Negative Breast Neoplasms/metabolism ; Triple Negative Breast Neoplasms/mortality ; Tumor Stem Cell Assay ; Tumor Suppressor Proteins/antagonists & inhibitors ; Tumor Suppressor Proteins/metabolism ; Up-Regulation
Chemical Substances	Antineoplastic Agents ; LIN9 protein, human ; Neoplasm Proteins ; Nuclear Proteins ; Taxoids ; Tumor Suppressor Proteins ; NEK2 protein, human (EC 2.7.11.1) ; NIMA-Related Kinases (EC 2.7.11.1) ; Paclitaxel (P88XT4IS4D)
Language	English
Publishing date	2020-02-13
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	1432-1
ISSN	1538-7445 ; 0008-5472
ISSN (online)	1538-7445
ISSN	0008-5472
DOI	10.1158/0008-5472.CAN-19-3466
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