Please use this identifier to cite or link to this item: https://doi.org/10.1038/cddis.2016.387
Title: Normalizing' the malignant phenotype of luminal breast cancer cells via alpha(v)beta(3)-integrin
Authors: Abu-Tayeh, H
Weidenfeld, K
Zhilin-Roth, A
Schif-Zuck, S
Thaler, S
Cotarelo, C
Tan, T.Z 
Thiery, J.P 
Green, J.E
Klorin, G
Sabo, E
Sleeman, J.P
Tzukerman, M
Barkan, D
Keywords: alpha6 integrin
CD24 antigen
cyclin dependent kinase inhibitor 1A
epithelial cell adhesion molecule
Notch4 receptor
vitronectin receptor
Notch receptor
NOTCH4 protein, human
oncoprotein
vitronectin receptor
animal experiment
animal model
apoptosis
Article
basement membrane
breast cancer cell line
breast carcinoma
breast epithelium
breast hyperplasia
cancer growth
cancer staging
cell differentiation
cell proliferation
controlled study
cytoplasm
down regulation
human
human tissue
intraductal carcinoma
luminal A breast cancer
mouse
nonhuman
nuclear size
phenotype
priority journal
protein expression
protein localization
three dimensional imaging
tumor differentiation
tumor microenvironment
acinar cell
breast tumor
cancer stem cell
cytoplasm
embryonic stem cell
female
gene silencing
hyperplasia
MCF-7 cell line
metabolism
multicellular spheroid
pathology
phenotype
signal transduction
teratoma
tumor cell line
Acinar Cells
Basement Membrane
Breast Neoplasms
Cell Differentiation
Cell Line, Tumor
Cell Proliferation
Down-Regulation
Embryonic Stem Cells
Female
Gene Knockdown Techniques
Humans
Hyperplasia
Integrin alphaVbeta3
MCF-7 Cells
Neoplastic Stem Cells
Organoids
Phenotype
Proto-Oncogene Proteins
Receptors, Notch
Signal Transduction
Spheroids, Cellular
Teratoma
Issue Date: 2016
Publisher: Nature Publishing Group
Citation: Abu-Tayeh, H, Weidenfeld, K, Zhilin-Roth, A, Schif-Zuck, S, Thaler, S, Cotarelo, C, Tan, T.Z, Thiery, J.P, Green, J.E, Klorin, G, Sabo, E, Sleeman, J.P, Tzukerman, M, Barkan, D (2016). Normalizing' the malignant phenotype of luminal breast cancer cells via alpha(v)beta(3)-integrin. Cell Death and Disease 7 (12) : e2491. ScholarBank@NUS Repository. https://doi.org/10.1038/cddis.2016.387
Abstract: Reestablishing tissue organization of breast cancer cells into acini was previously shown to override their malignant phenotype. In our study, we demonstrate that alpha(v)beta(3) integrin (Int-?v?3), previously shown to play a role in cancer progression, promoted differentiation and growth arrest of organoids derived from luminal A breast cancer cells grown in their relevant three-dimensional microenvironment. These organoids differentiated into normal-like acini resembling a benign stage of breast tissue. Likewise, we demonstrate that Int-?v?3 is selectively expressed in the epithelium of the benign stage of breast tissues, and is lost during the early stages of luminal A breast cancer progression. Notably, the organoids' reversion into normal-like acini was mediated by cancer luminal progenitor-like cells expressing both EpCAM high CD49f low CD24 + and Int-?v?3. Furthermore, downregulation of Notch4 expression and downstream signaling was shown to mediate Int-?v?3-induced reversion. Intriguingly, when luminal A breast cancer cells expressing Int-?v?3 were injected into a humanized mouse model, differentiated tumors developed when compared with that generated by control cells. Hence, our data suggest that promoting differentiation of luminal A breast cancer cells by signaling emanating from Int-?v?3 can potentially promote 'normalization' of their malignant phenotype and may prevent the malignant cells from progressing. © 2016 The Author (S).
Source Title: Cell Death and Disease
URI: https://scholarbank.nus.edu.sg/handle/10635/174910
ISSN: 20414889
DOI: 10.1038/cddis.2016.387
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