Membrane to cortex attachment determines different mechanical phenotypes in LGR5+ and LGR5- colorectal cancer cells

Conti S, Venturini V, Cañellas-Socias A, Cortina C, Abenza JF, Stephan-Otto Attolini C, Middendorp Guerra E, Xu CK, Li JH, Rossetti L, Stassi G, Roca-Cusachs P, Diz-Muñoz A, Ruprecht V, Guck J, Batlle E, Labernadie A, Trepat X (2024)

Publication Type: Journal article

Publication year: 2024

Journal

Nature Communications Nature Publishing Group: Nature Communications

Book Volume: 15

Article Number: 3363

Journal Issue: 1

DOI: 10.1038/s41467-024-47227-2

Abstract

Colorectal cancer (CRC) 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 poorly understood. Using CRC patient derived organoids (PDOs), we find 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 single cell RNA-sequencing (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.

Authors with CRIS profile

Jochen Guck

Involved external institutions

Institute for Research in Biomedicine / IRB Barcelona ES Spain (ES) Max-Planck-Institut für die Physik des Lichts (MPL) / Max Planck Institute for the Science of Light DE Germany (DE) European Molecular Biology Laboratory (EMBL) DE Germany (DE) Instituto de Bioingeniería de Cataluña / Institute for Bioengineering of Catalonia ES Spain (ES) Centre for Genomic Regulation (CRG) ES Spain (ES) Università degli Studi di Palermo IT Italy (IT)

How to cite

APA:

Conti, S., Venturini, V., Cañellas-Socias, A., Cortina, C., Abenza, J.F., Stephan-Otto Attolini, C.,... Trepat, X. (2024). Membrane to cortex attachment determines different mechanical phenotypes in LGR5+ and LGR5- colorectal cancer cells. Nature Communications, 15(1). https://doi.org/10.1038/s41467-024-47227-2

MLA:

Conti, Sefora, et al. "Membrane to cortex attachment determines different mechanical phenotypes in LGR5+ and LGR5- colorectal cancer cells." Nature Communications 15.1 (2024).

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