Basal-like breast carcinoma is characterized by poor prognosis and high intratumour heterogeneity. In an immortalized basal-like breast epithelial cell line, we identified two anticorrelated gene-expression programs that arise among single extracellular matrix (ECM)-attached cells during organotypic three-dimensional culture. The first contains multiple TGF-β-related genes including TGFBR3, whereas the second contains JUND and the basal-like marker KRT5. TGFBR3 and JUND interconnect through four negative-feedback loops to form a circuit that exhibits spontaneous damped oscillations in three-dimensional culture. The TGFBR3–JUND circuit is conserved in some premalignant lesions that heterogeneously express KRT5. The circuit depends on ECM engagement, as detachment causes a rewiring that is triggered by RPS6 dephosphorylation and maintained by juxtacrine tenascin C, which is critical for intraductal colonization of basal-like breast cancer cells in vivo. Intratumour heterogeneity need not stem from partial differentiation and could instead reflect dynamic toggling of cells between expression states that are not cell autonomous.
%0 Journal Article
%1 wang2014matrixdependent
%A Wang, Chun-Chao
%A Bajikar, Sameer S.
%A Jamal, Leen
%A Atkins, Kristen A.
%A Janes, Kevin A.
%D 2014
%I Nature Publishing Group
%J Nat Cell Biol
%K ECM basal-like breast carcinoma circuit for_Josh from_Libin regulatory
%N 4
%P 345--356
%T A time- and matrix-dependent TGFBR3–JUND–KRT5 regulatory circuit in single breast epithelial cells and basal-like premalignancies
%U http://dx.doi.org/10.1038/ncb2930
%V 16
%X Basal-like breast carcinoma is characterized by poor prognosis and high intratumour heterogeneity. In an immortalized basal-like breast epithelial cell line, we identified two anticorrelated gene-expression programs that arise among single extracellular matrix (ECM)-attached cells during organotypic three-dimensional culture. The first contains multiple TGF-β-related genes including TGFBR3, whereas the second contains JUND and the basal-like marker KRT5. TGFBR3 and JUND interconnect through four negative-feedback loops to form a circuit that exhibits spontaneous damped oscillations in three-dimensional culture. The TGFBR3–JUND circuit is conserved in some premalignant lesions that heterogeneously express KRT5. The circuit depends on ECM engagement, as detachment causes a rewiring that is triggered by RPS6 dephosphorylation and maintained by juxtacrine tenascin C, which is critical for intraductal colonization of basal-like breast cancer cells in vivo. Intratumour heterogeneity need not stem from partial differentiation and could instead reflect dynamic toggling of cells between expression states that are not cell autonomous.
@article{wang2014matrixdependent,
abstract = {Basal-like breast carcinoma is characterized by poor prognosis and high intratumour heterogeneity. In an immortalized basal-like breast epithelial cell line, we identified two anticorrelated gene-expression programs that arise among single extracellular matrix (ECM)-attached cells during organotypic three-dimensional culture. The first contains multiple TGF-β-related genes including TGFBR3, whereas the second contains JUND and the basal-like marker KRT5. TGFBR3 and JUND interconnect through four negative-feedback loops to form a circuit that exhibits spontaneous damped oscillations in three-dimensional culture. The TGFBR3–JUND circuit is conserved in some premalignant lesions that heterogeneously express KRT5. The circuit depends on ECM engagement, as detachment causes a rewiring that is triggered by RPS6 dephosphorylation and maintained by juxtacrine tenascin C, which is critical for intraductal colonization of basal-like breast cancer cells in vivo. Intratumour heterogeneity need not stem from partial differentiation and could instead reflect dynamic toggling of cells between expression states that are not cell autonomous.},
added-at = {2014-04-22T23:16:13.000+0200},
author = {Wang, Chun-Chao and Bajikar, Sameer S. and Jamal, Leen and Atkins, Kristen A. and Janes, Kevin A.},
biburl = {https://www.bibsonomy.org/bibtex/2d55517fea98d0ad0cb46a817c5ecb649/ubcmathbio},
interhash = {4b86ea91932cbc3ade058420ba670932},
intrahash = {d55517fea98d0ad0cb46a817c5ecb649},
issn = {14657392},
journal = {Nat Cell Biol},
keywords = {ECM basal-like breast carcinoma circuit for_Josh from_Libin regulatory},
month = apr,
number = 4,
pages = {345--356},
publisher = {Nature Publishing Group},
timestamp = {2014-04-23T08:27:33.000+0200},
title = {A time- and matrix-dependent TGFBR3–JUND–KRT5 regulatory circuit in single breast epithelial cells and basal-like premalignancies},
url = {http://dx.doi.org/10.1038/ncb2930},
volume = 16,
year = 2014
}