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Open Access 01-12-2024 | Colon Cancer | Research

The Hippo pathway terminal effector TAZ/WWTR1 mediates oxaliplatin sensitivity in p53 proficient colon cancer cells

Authors: Věra Slaninová, Lisa Heron-Milhavet, Mathilde Robin, Laura Jeanson, Adam Aissanou, Diala Kantar, Diego Tosi, Laurent Bréhélin, Céline Gongora, Alexandre Djiane

Published in: BMC Cancer | Issue 1/2024

Abstract

YAP and TAZ, the Hippo pathway terminal transcriptional activators, are frequently upregulated in cancers. In tumor cells, they have been mainly associated with increased tumorigenesis controlling different aspects from cell cycle regulation, stemness, or resistance to chemotherapies. In fewer cases, they have also been shown to oppose cancer progression, including by promoting cell death through the action of the p73/YAP transcriptional complex, in particular after chemotherapeutic drug exposure. Using HCT116 cells, we show here that oxaliplatin treatment led to core Hippo pathway down-regulation and nuclear accumulation of TAZ. We further show that TAZ was required for the increased sensitivity of HCT116 cells to oxaliplatin, an effect that appeared independent of p73, but which required the nuclear relocalization of TAZ. Accordingly, Verteporfin and CA3, two drugs affecting the activity of YAP and TAZ, showed antagonistic effects with oxaliplatin in co-treatments. Importantly, using several colorectal cell lines, we show that the sensitizing action of TAZ to oxaliplatin is dependent on the p53 status of the cells. Our results support thus an early action of TAZ to sensitize cells to oxaliplatin, consistent with a model in which nuclear TAZ in the context of DNA damage and p53 activity pushes cells towards apoptosis.

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Title: The Hippo pathway terminal effector TAZ/WWTR1 mediates oxaliplatin sensitivity in p53 proficient colon cancer cells
Authors: Věra Slaninová
Lisa Heron-Milhavet
Mathilde Robin
Laura Jeanson
Adam Aissanou
Diala Kantar
Diego Tosi
Laurent Bréhélin
Céline Gongora
Alexandre Djiane
Publication date: 01-12-2024
Publisher: BioMed Central
Keywords: Colon Cancer
Colon Cancer
Dasatinib
Published in: BMC Cancer / Issue 1/2024
Electronic ISSN: 1471-2407
DOI: https://doi.org/10.1186/s12885-024-12316-4

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