生物
癌症干细胞
间充质干细胞
干细胞
自分泌信号
细胞生物学
癌症研究
上皮-间质转换
转移
细胞
细胞迁移
癌细胞
癌症
细胞培养
遗传学
作者
Arthur W. Lambert,Christopher Fiore,Yogesh Chutake,Elisha R Verhaar,Patrick C Strasser,Mei Wei Chen,Daneyal Farouq,Sunny Das,Xin Li,Elinor Ng Eaton,Yun Zhang,Joana Liu Donaher,Ian A. Engstrom,Ferenc Reinhardt,Bingbing Yuan,Sumeet Gupta,Bruce M. Wollison,Matthew L. Eaton,Brian Bierie,John P. Carulli,Eric R. Olson,Matthew G. Guenther,Robert A. Weinberg
标识
DOI:10.1016/j.devcel.2022.11.015
摘要
Cancer stem cells (CSCs) may serve as the cellular seeds of tumor recurrence and metastasis, and they can be generated via epithelial-mesenchymal transitions (EMTs). Isolating pure populations of CSCs is difficult because EMT programs generate multiple alternative cell states, and phenotypic plasticity permits frequent interconversions between these states. Here, we used cell-surface expression of integrin β4 (ITGB4) to isolate highly enriched populations of human breast CSCs, and we identified the gene regulatory network operating in ITGB4+ CSCs. Specifically, we identified ΔNp63 and p73, the latter of which transactivates ΔNp63, as centrally important transcriptional regulators of quasi-mesenchymal CSCs that reside in an intermediate EMT state. We found that the transcriptional program controlled by ΔNp63 in CSCs is largely distinct from the one that it orchestrates in normal basal mammary stem cells and, instead, it more closely resembles a regenerative epithelial stem cell response to wounding. Moreover, quasi-mesenchymal CSCs repurpose this program to drive metastatic colonization via autocrine EGFR signaling.
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