%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 }