Mechanisms of cellular crosstalk in the gastric tumor microenvironment are mediated by YAP1 and STAT3

Pathum Thilakasiri; Ryan N. O’keefe; Sarah Q. To; David Chisanga; Moritz F. Eissmann; Annalisa L.E. Carli; Belinda Duscio; David Baloyan; Rhynelle S. Dmello; David Williams; John Mariadason; Ashleigh R. Poh; Bhupinder Pal; Benjamin T. Kile; Joseph H.A. Vissers; Kieran F. Harvey; Michael Buchert; Wei Shi; Matthias Ernst; Ashwini L. Chand

doi:10.26508/lsa.202302411

Mechanisms of cellular crosstalk in the gastric tumor microenvironment are mediated by YAP1 and STAT3

Pathum Thilakasiri, Ryan N. O’keefe, Sarah Q. To, David Chisanga, Moritz F. Eissmann, Annalisa L.E. Carli, Belinda Duscio, David Baloyan, Rhynelle S. Dmello, David Williams, John Mariadason, Ashleigh R. Poh, Bhupinder Pal, Benjamin T. Kile, Joseph H.A. 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.

Original language	English
Article number	e202302411
Number of pages	17
Journal	Life Science Alliance
Volume	7
Issue number	2
DOIs	https://doi.org/10.26508/lsa.202302411
Publication status	Published - Feb 2024

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10.26508/lsa.202302411Licence: CC BY

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Thilakasiri, P., O’keefe, R. N., To, S. Q., Chisanga, D., Eissmann, M. F., Carli, A. L. E., Duscio, B., Baloyan, D., Dmello, R. S., Williams, D., Mariadason, J., Poh, A. R., Pal, B., Kile, B. T., Vissers, J. H. A., Harvey, K. F., Buchert, M., Shi, W., Ernst, M., & Chand, A. L. (2024). Mechanisms of cellular crosstalk in the gastric tumor microenvironment are mediated by YAP1 and STAT3. Life Science Alliance, 7(2), Article e202302411. https://doi.org/10.26508/lsa.202302411

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title = "Mechanisms of cellular crosstalk in the gastric tumor microenvironment are mediated by YAP1 and STAT3",

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.",

author = "Pathum Thilakasiri and O{\textquoteright}keefe, {Ryan N.} and To, {Sarah Q.} and David Chisanga and Eissmann, {Moritz F.} and Carli, {Annalisa L.E.} and Belinda Duscio and David Baloyan and Dmello, {Rhynelle S.} and David Williams and John Mariadason and Poh, {Ashleigh R.} and Bhupinder Pal and Kile, {Benjamin T.} and Vissers, {Joseph H.A.} and Harvey, {Kieran F.} and Michael Buchert and Wei Shi and Matthias Ernst and Chand, {Ashwini L.}",

note = "Funding Information: We acknowledge the support of the Victorian State Government Operational Infrastructure Support, the National Medical Health and Research Council (NHMRC) of Australia, Cancer Council Victoria, and the Victoria Cancer Agency. This work was supported in part by an NHMRC Program Grant 1092788 (to M Ernst) and by fellowships from the Victorian Cancer Agency 19014 (to AL Chand) and the NHMRC Fellowship 1062247 (to AL Chand). Publisher Copyright: {\textcopyright} 2023 Thilakasiri et al.",

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month = feb,

doi = "10.26508/lsa.202302411",

language = "English",

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Thilakasiri, P, O’keefe, RN, To, SQ, Chisanga, D, Eissmann, MF, Carli, ALE, Duscio, B, Baloyan, D, Dmello, RS, Williams, D, Mariadason, J, Poh, AR, Pal, B, Kile, BT, Vissers, JHA, Harvey, KF, Buchert, M, Shi, W, Ernst, M & Chand, AL 2024, 'Mechanisms of cellular crosstalk in the gastric tumor microenvironment are mediated by YAP1 and STAT3', Life Science Alliance, vol. 7, no. 2, e202302411. https://doi.org/10.26508/lsa.202302411

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AU - Thilakasiri, Pathum

AU - O’keefe, Ryan N.

AU - To, Sarah Q.

AU - Chisanga, David

AU - Eissmann, Moritz F.

AU - Carli, Annalisa L.E.

AU - Duscio, Belinda

AU - Baloyan, David

AU - Dmello, Rhynelle S.

AU - Williams, David

AU - Mariadason, John

AU - Poh, Ashleigh R.

AU - Pal, Bhupinder

AU - Kile, Benjamin T.

AU - Vissers, Joseph H.A.

AU - Harvey, Kieran F.

AU - Buchert, Michael

AU - Shi, Wei

AU - Ernst, Matthias

AU - Chand, Ashwini L.

N1 - Funding Information: We acknowledge the support of the Victorian State Government Operational Infrastructure Support, the National Medical Health and Research Council (NHMRC) of Australia, Cancer Council Victoria, and the Victoria Cancer Agency. This work was supported in part by an NHMRC Program Grant 1092788 (to M Ernst) and by fellowships from the Victorian Cancer Agency 19014 (to AL Chand) and the NHMRC Fellowship 1062247 (to AL Chand). Publisher Copyright: © 2023 Thilakasiri et al.

PY - 2024/2

Y1 - 2024/2

N2 - 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.

AB - 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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SN - 2575-1077

VL - 7

JO - Life Science Alliance

JF - Life Science Alliance

IS - 2

M1 - e202302411

ER -

Mechanisms of cellular crosstalk in the gastric tumor microenvironment are mediated by YAP1 and STAT3

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New Targeted Therapies in Breast Cancer

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Mechanisms of cellular crosstalk in the gastric tumor microenvironment are mediated by YAP1 and STAT3

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New Targeted Therapies in Breast Cancer

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