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Translational Therapeutics

RE: Reply to Rio-Vilariño and colleagues’ article and misconception about YAP1 Ser 397 phosphorylation function

British Journal of Cancer volume 130, page 1892 (2024)Cite this article

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Dear Dr. Evans,

I read the article titled “Inhibition of the AURKA/YAP1 axis is a promising therapeutic option for overcoming cetuximab resistance in colorectal cancer stem cells,” published by Rio-Vilariño and colleagues [1] in the last issue of the British Journal of Cancer. While the title is enticing, the interpretation of the study could be spurious. The authors interpret that YAP1 Ser 397 phosphorylation activates YAP; however, this assertion is not correct. The Hippo signalling pathway negatively regulates the transcriptional coactivator YAP1 through LATS-mediated phosphorylation at two sites: Ser 127 and Ser 397, which drive YAP inactivation. LATS phosphorylation at serine 127 promotes YAP1 cytoplasmic retention, while phosphorylation at serine 397 creates a phosphodegron that signals for β-TrCP-driven E3 ligase-mediated degradation [2]. To confirm YAP1 activation, it is important to assess the expression of downstream representative genes such as CYR61. I recommend that the authors revisit their findings and carefully reinterpret them.

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References

  1. Rio-Vilariño A, Cenigaonandia-Campillo A, García-Bautista A, Mateos-Gómez P, Schlaepfer MI, Del Puerto-Nevado L, et al. Inhibition of the AURKA/YAP1 axis is a promising therapeutic option for overcoming cetuximab resistance in colorectal cancer stem cells. Br J Cancer. 2024;130:1402–13.

    Article  PubMed  PubMed Central  Google Scholar 

  2. Piccolo S, Dupont S, Cordenonsi M. The biology of YAP/TAZ: hippo signaling and beyond. Physiol Rev. 2014;94:1287–312.

    Article  CAS  PubMed  Google Scholar 

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  1. IOR, Dr. Rosell Oncology Institute, Dexeus University Hospital, 08028, Barcelona, Spain

    Rafael Rosell

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  1. Rafael Rosell
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Conceptualisation, Writing original draft, review & editing: RR.

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Correspondence to Rafael Rosell.

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Rosell, R. RE: Reply to Rio-Vilariño and colleagues’ article and misconception about YAP1 Ser 397 phosphorylation function. Br J Cancer 130, 1892 (2024). https://doi.org/10.1038/s41416-024-02720-9

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