Authors
Binwu Tang, Jacob Minin, Victoria M Gonzalez, Zoya Z Khan, Andrew R Gaines, Yuval Raviv, Yu-An Yang, Christine P Carney, Zachary G Millman, Daniel Grun, Cristiana M Pineda, Alina Sharma, Dominic Esposito, Hualong Yan, Jing Huang, Andy D Tran, Michael Kruhlak, Howard H Yang, Maxwell P Lee, Lalage M Wakefield
Published in
Nature cell biology. Jul 27, 2026. Epub Jul 27, 2026.
Abstract
Cancer stem cells (CSCs) drive metastasis and therapy resistance, yet their behaviour within the complex tumour microenvironment remains poorly understood. Here we use a fluorescent reporter that marks CSCs to show that CSCs and their more differentiated progeny display strikingly different population dynamics during metastatic lung colonization in breast cancer models. CSC expansion is rapidly curtailed early in colonization, suggesting a strong negative feedback mechanism acting selectively on this subpopulation. We showed that CSCs are exceptionally sensitive to local microenvironmental cues such as cell crowding and nutrient availability. They respond earlier and more extensively than their differentiated progeny, thereby coupling tumour growth to resource and space availability. Microenvironmental signals converge on the transcriptional regulatory complex YAP/TAZ/TEAD, with CSC sensitivity arising from elevated signal reception and greater chromatin accessibility at TEAD-regulated enhancers. Targeting upstream inputs to this pathway reversed chemotherapy-induced CSC enrichment in lung metastases, suggesting a potential therapeutic strategy.
PMID:
42509263
Bibliographic data and abstract were imported from PubMed on 28 Jul 2026.
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