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Theses

TGFβ Controls the Apico-Basolateral Orientation of Tumor Spheres and Is Correlated With Patient Outcome in Colorectal Cancer

Abstract : The metastatic dissemination of cancer remains a major issue in patients’ treatment. Cell biology approaches, such as organoids, have the potential to bridge histological and molecular analyses to decipher the onco-morphogenetic programs that fuel cancer dissemination. The systematic prospective analysis of peritoneal effusions from patients with colorectal carcinoma (CRC) identified new tumoral intermediates called Tumour Spheres with Inverted polarity (TSIPs). TSIPs are cell clusters mediating the metastatic spread of CRC evolving from the serrated pathway, but their underlying biology is unknown. While all TSIPs harbor an inverted apico-basolateral polarity in fluids, here, we report two distinct topologies in tissues and organotypic culture: TSIPs either conserve the inverted “apical-out” polarity or switch to a conventional “apical-in” polarity. We identified TGFβ and focal adhesion signaling as the main drivers of polarity orientation. Moreover, the automated assessment of these phenotypes and the calculation of a polarity score proved that the apical-out histology is associated with poor patient survival. This study identifies new tumour cell behaviors and their associated oncogenic pathways that could be exploited to stratify mucinous CRC patients with high risk of metastatic spread.
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https://tel.archives-ouvertes.fr/tel-03273375
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Submitted on : Tuesday, June 29, 2021 - 10:58:09 AM
Last modification on : Friday, July 9, 2021 - 3:30:11 PM

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Charlotte Canet-Jourdan. TGFβ Controls the Apico-Basolateral Orientation of Tumor Spheres and Is Correlated With Patient Outcome in Colorectal Cancer. Cancer. Université Paris-Saclay, 2021. English. ⟨NNT : 2021UPASL030⟩. ⟨tel-03273375⟩

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