| Added by | adjiane.lab |
|---|---|
| Last modified by | ircm doc |
| Group name | EquipeAD |
| Item Type | Journal Article |
| Title | The Hippo pathway terminal effector TAZ/WWTR1 mediates oxaliplatin sensitivity in p53 proficient colon cancer cells |
| Creator | Slaninová et al. |
| Author | V?ra Slaninová |
| Author | Lisa Heron-Milhavet |
| Author | Mathilde Robin |
| Author | Laura Jeanson |
| Author | Adam Aissanou |
| Author | Diala Kantar |
| Author | Diego Tosi |
| Author | Laurent Bréhélin |
| Author | Céline Gongora |
| Author | Alexandre Djiane |
| 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. |
| Publication | BMC cancer |
| Volume | 24 |
| Issue | 1 |
| Pages | 587 |
| Date | 2024-05-14 |
| Journal Abbr | BMC Cancer |
| Language | eng |
| DOI | 10.1186/s12885-024-12316-4 |
| ISSN | 1471-2407 |
| Library Catalog | PubMed |
| Extra | PMID: 38741073 PMCID: PMC11092100 |
| Tags | Adaptor Proteins, Signal Transducing, Antineoplastic Agents, Apoptosis, arc, Cell Line, Tumor, Colonic Neoplasms, DNA-Binding Proteins, Drug Resistance, Neoplasm, first-last-corresponding, Gene Expression Regulation, Neoplastic, gso, HCT116 Cells, Hippo signaling, Hippo Signaling Pathway, Humans, Intracellular Signaling Peptides and Proteins, ligue, mab, mabimprove, Nuclear Proteins, Organoplatinum Compounds, original, p53, phd, Porphyrins, postdoc, premium_IRCM, Protein Serine-Threonine Kinases, Signal Transduction, siric, TAZ, Trans-Activators, Transcription Factors, Transcriptional Coactivator with PDZ-Binding Motif Proteins, Tumor Protein p73, Tumor Suppressor Protein p53, Tumor Suppressor Proteins, Verteporfin, YAP-Signaling Proteins |
| Date Added | 2024/09/30 - 01:10:15 |
| Date Modified | 2025/01/10 - 10:02:29 |
| Notes and Attachments | Full Text (Attachment) PubMed entry (Attachment) |
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