Patient-derived organoids identify an apico-basolateral polarity switch associated with survival in colorectal cancer - Compartimentation et dynamique cellulaires Accéder directement au contenu
Article Dans Une Revue Journal of Cell Science Année : 2022

Patient-derived organoids identify an apico-basolateral polarity switch associated with survival in colorectal cancer

Joel Raingeaud
  • Fonction : Auteur
  • PersonId : 1117110
Patrick Gonin

Résumé

The metastatic progression of cancer remains a major issue in patient treatment. However, the molecular and cellular mechanisms underlying this process remain unclear. Here, we use primary explants and organoids from patients harboring mucinous colorectal carcinoma (MUC CRC), a poor-prognosis histological form of digestive cancer, to study the architecture, invasive behavior and chemoresistance of tumor cell intermediates. We report that these tumors maintain a robust apico-basolateral polarity as they spread in the peritumoral stroma or organotypic collagen-I gels. We identified two distinct topologies – MUC CRCs either display a conventional ‘apical-in’ polarity or, more frequently, harbor an inverted ‘apical-out’ topology. Transcriptomic analyses combined with interference experiments on organoids showed that TGFβ and focal adhesion signaling pathways are the main drivers of polarity orientation. Finally, we show that the apical-out topology is associated with increased resistance to chemotherapeutic treatments in organoids and decreased patient survival in the clinic. Thus, studies on patient-derived organoids have the potential to bridge histological, cellular and molecular analyses to decrypt onco-morphogenic programs and stratify cancer patients. This article has an associated First Person interview with the first author of the paper.
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Dates et versions

hal-03808144 , version 1 (20-10-2022)

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Charlotte Canet-Jourdan, Diane-Laure Pagès, Clémence Nguyen-Vigouroux, Jérôme Cartry, Olivier Zajac, et al.. Patient-derived organoids identify an apico-basolateral polarity switch associated with survival in colorectal cancer. Journal of Cell Science, 2022, 135 (14), pp.jcs259256. ⟨10.1242/jcs.259256⟩. ⟨hal-03808144⟩
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