Bota-Rabassedas, NeusBanerjee, PriyamNiu, YichiCao, WenjianLuo, JiayiXi, YuanxinTan, XiaochaoSheng, KuanweiAhn, Young-HoLee, SieunParra, Edwin RogerRodriguez-Canales, JaimeAlbritton, JacobWeiger, MichaelLiu, XinGuo, Hou-FuYu, JiangRodriguez, B. LeticiaFirestone, Joshua J.A.Mino, BarbaraCreighton, Chad J.Solis, Luisa M.Villalobos, PamelaRaso, Maria GabrielaSazer, Daniel W.Gibbons, Don L.Russell, William K.Longmore, Gregory D.Wistuba, Ignacio I.Wang, JingChapman, Harold A.Miller, Jordan S.Zong, ChenghangKurie, Jonathan M.2021-05-072021-05-072021Bota-Rabassedas, Neus, Banerjee, Priyam, Niu, Yichi, et al.. "Contextual cues from cancer cells govern cancer-associated fibroblast heterogeneity." <i>Cell Reports,</i> 35, no. 3 (2021) Cell Press: https://doi.org/10.1016/j.celrep.2021.109009.https://hdl.handle.net/1911/110487Cancer cells function as primary architects of the tumor microenvironment. However, the molecular features of cancer cells that govern stromal cell phenotypes remain unclear. Here, we show that cancer-associated fibroblast (CAF) heterogeneity is driven by lung adenocarcinoma (LUAD) cells at either end of the epithelial-to-mesenchymal transition (EMT) spectrum. LUAD cells that have high expression of the EMT-activating transcription factor ZEB1 reprogram CAFs through a ZEB1-dependent secretory program and direct CAFs to the tips of invasive projections through a ZEB1-driven CAF repulsion process. The EMT, in turn, sensitizes LUAD cells to pro-metastatic signals from CAFs. Thus, CAFs respond to contextual cues from LUAD cells to promote metastasis.engThis is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).Journal article1-s2-0-S2211124721003235-mainhttps://doi.org/10.1016/j.celrep.2021.109009