LGR5型
下调和上调
癌症干细胞
干细胞
埃兹林
结直肠癌
表型
细胞外基质
癌细胞
转移
细胞生物学
生物
癌症
癌症研究
病理
细胞
医学
细胞骨架
遗传学
基因
作者
Sefora Conti,Valeria Venturini,Adrià Cañellas-Socias,Carme Cortina,Juan F. Abenza,Camille Stephan‐Otto Attolini,Emily Middendorp Guerra,Catherine Xu,Jia Hui Li,Leone Rossetti,Giorgio Stassi,Pere Roca‐Cusachs,Alba Diz-Muñoz,Verena Ruprecht,Jochen Guck,Eduard Batlle,Anna Labernadie,Xavier Trepat
标识
DOI:10.1101/2023.12.04.569244
摘要
Colorectal cancer tumors are composed of heterogeneous and plastic cell populations, including a pool of cancer stem cells that express LGR5. Whether these distinct cell populations display different mechanical properties, and how these properties might contribute to metastasis is unknown. Using CRC patient derived organoids (PDOs), we found that compared to LGR5- cells, LGR5+ cancer stem cells are stiffer, adhere better to the extracellular matrix (ECM), move slower both as single cells and clusters, display higher nuclear YAP, show a higher survival rate in response to mechanical confinement, and form larger transendothelial gaps. These differences are largely explained by the downregulation of the membrane to cortex attachment proteins Ezrin/Radixin/Moesin (ERMs) in the LGR5+ cells. By analyzing scRNA-seq expression patterns from a patient cohort, we show that this downregulation is a robust signature of colorectal tumors. Our results show that LGR5- cells display a mechanically dynamic phenotype suitable for dissemination from the primary tumor whereas LGR5+ cells display a mechanically stable and resilient phenotype suitable for extravasation and metastatic growth.
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