Mechanisms of cellular crosstalk in the gastric tumor microenvironment are mediated by YAP1 and STAT3
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(Published version)
Date
2024
Authors
Thilakasiri, P.
O'Keefe, R.N.
To, S.Q.
Chisanga, D.
Eissmann, M.F.
Carli, A.L.
Duscio, B.
Baloyan, D.
Dmello, R.S.
Williams, D.
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Journal article
Citation
Life Science Alliance, 2024; 7(2):e202302411-1-e202302411-17
Statement of Responsibility
Pathum Thilakasiri, Ryan N O, Keefe, Sarah Q To, David Chisanga, Moritz F Eissmann, Annalisa LE Carli, Belinda Duscio, David Baloyan, Rhynelle S Dmello, David Williams, John Mariadason, Ashleigh R Poh, Bhupinder Pal, Benjamin T Kile, Joseph HA Vissers, Kieran F Harvey, Michael Buchert, Wei Shi, Matthias Ernst, Ashwini L Chand
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Abstract
Deregulation of the Hippo pathway is a driver for cancer progression and treatment resistance. In the context of gastric cancer, YAP1 is a biomarker for poor patient prognosis. Although genomic tumor profiling provides information of Hippo pathway activation, the present study demonstrates that inhibition of Yap1 activity has anti-tumor effects in gastric tumors driven by oncogenic mutations and inflammatory cytokines. We show that Yap1 is a key regulator of cell metabolism, proliferation, and immune responses in normal and neoplastic gastric epithelium. We propose that the Hippo pathway is targetable across gastric cancer subtypes and its therapeutic benefits are likely to be mediated by both cancer cell-intrinsic and -extrinsic mechanisms.
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Published online: 13 November, 2023
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© 2023 Thilakasiri et al. License: This article is available under a Creative Commons License (Attribution 4.0 International, as described at https://creativecommons.org/licenses/by/4.0/).