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Conference Paper: Functional and mechanistic characterization of ΔNp63α in esophageal squamous cell carcinoma

TitleFunctional and mechanistic characterization of ΔNp63α in esophageal squamous cell carcinoma
Authors
Issue Date2022
PublisherAmerican Association for Cancer Research. The Journal's web site is located at http://cancerres.aacrjournals.org/
Citation
Proceedings of the American Association for Cancer Research (AACR) Annual Meeting, New Orleans, USA, 8-13 April,2022. In Cancer Research, 2022, v. 82 n. 12, Suppl., abstract 5835: How to Cite?
AbstractEsophageal squamous cell carcinoma (ESCC) is highly prevalent in Asia with a poor prognosis and a high mortality rate [1, 2]. The p63 protein, encoded by TP63, is a master regulator involved in many cell events including cell cycle, DNA damage, cell proliferation, stem cell maintenance, and cell death in different cancer types. ΔNp63α is the dominantly expressed isoform of p63 in squamous cell carcinomas, playing a critical role in tumorigenesis [3, 4]. However, the functional roles of ΔNp63α in ESCC have not been fully elucidated. Our results have revealed that ΔNp63α is highly expressed and up-regulated in ESCC. We have shown that ΔNp63α protein expression plays an oncogenic role in ESCC cells, depletion of which inhibits in vitro cell proliferation and colony formation and greatly suppresses in vivo tumor growth, in a panel of ESCC cell lines and our latest patient-derived organoid cultures, potentially in a differentiation-dependent manner. Glycolysis pathway and two novel downstream signaling pathways of ΔNp63α, MYC/4EBP1 and AKT/NDRG1, are significantly suppressed upon ΔNp63α depletion in ESCC cell lines. Notably, xenografts of ΔNp63α-depleted human ESCC cells show elevated infiltrating cancer-associated fibroblasts (CAFs), which may contribute to tumor suppression by ΔNp63α depletion. These data not only shed light on the ΔNp63α functions and how they contribute to the ESCC tumorigenesis, but also unravel potential therapeutic benefits for ESCC patients in the future. Acknowledgements: We acknowledge DSMZ (German Collection of Microorganisms and Cell Culture) for the KYSE cell lines. We acknowledge the Research Grants Council Theme-Based Research Scheme grant T12-701/17-R to MLL. References [1] Chen, W., et al., Cancer statistics in China, 2015. CA Cancer J Clin, 2016. 66(2): p. 115-32. [2] Peng, L., et al., CCGD-ESCC: A Comprehensive Database for Genetic Variants Associated with Esophageal Squamous Cell Carcinoma in Chinese Population. Genomics Proteomics Bioinformatics, 2018. 16(4): p. 262-268. [3] Fukunishi, N., et al., Induction of DeltaNp63 by the newly identified keratinocyte-specific transforming growth factor beta Signaling Pathway with Smad2 and IkappaB Kinase alpha in squamous cell carcinoma. Neoplasia, 2010. 12(12): p. 969-79. [4] Moses, M.A., et al., Molecular Mechanisms of p63-Mediated Squamous Cancer Pathogenesis. Int J Mol Sci, 2019. 20(14).
DescriptionE-Poster - Session OPO.MCB03.01 - Oncogenes and Tumor Suppressor Genes - abstract no. 5835
Persistent Identifierhttp://hdl.handle.net/10722/313572
ISSN
2023 Impact Factor: 12.5
2023 SCImago Journal Rankings: 3.468

 

DC FieldValueLanguage
dc.contributor.authorSO, SS-
dc.contributor.authorYu, Z-
dc.contributor.authorLaw, SYK-
dc.contributor.authorLung, ML-
dc.date.accessioned2022-06-17T06:48:23Z-
dc.date.available2022-06-17T06:48:23Z-
dc.date.issued2022-
dc.identifier.citationProceedings of the American Association for Cancer Research (AACR) Annual Meeting, New Orleans, USA, 8-13 April,2022. In Cancer Research, 2022, v. 82 n. 12, Suppl., abstract 5835:-
dc.identifier.issn0008-5472-
dc.identifier.urihttp://hdl.handle.net/10722/313572-
dc.descriptionE-Poster - Session OPO.MCB03.01 - Oncogenes and Tumor Suppressor Genes - abstract no. 5835-
dc.description.abstractEsophageal squamous cell carcinoma (ESCC) is highly prevalent in Asia with a poor prognosis and a high mortality rate [1, 2]. The p63 protein, encoded by TP63, is a master regulator involved in many cell events including cell cycle, DNA damage, cell proliferation, stem cell maintenance, and cell death in different cancer types. ΔNp63α is the dominantly expressed isoform of p63 in squamous cell carcinomas, playing a critical role in tumorigenesis [3, 4]. However, the functional roles of ΔNp63α in ESCC have not been fully elucidated. Our results have revealed that ΔNp63α is highly expressed and up-regulated in ESCC. We have shown that ΔNp63α protein expression plays an oncogenic role in ESCC cells, depletion of which inhibits in vitro cell proliferation and colony formation and greatly suppresses in vivo tumor growth, in a panel of ESCC cell lines and our latest patient-derived organoid cultures, potentially in a differentiation-dependent manner. Glycolysis pathway and two novel downstream signaling pathways of ΔNp63α, MYC/4EBP1 and AKT/NDRG1, are significantly suppressed upon ΔNp63α depletion in ESCC cell lines. Notably, xenografts of ΔNp63α-depleted human ESCC cells show elevated infiltrating cancer-associated fibroblasts (CAFs), which may contribute to tumor suppression by ΔNp63α depletion. These data not only shed light on the ΔNp63α functions and how they contribute to the ESCC tumorigenesis, but also unravel potential therapeutic benefits for ESCC patients in the future. Acknowledgements: We acknowledge DSMZ (German Collection of Microorganisms and Cell Culture) for the KYSE cell lines. We acknowledge the Research Grants Council Theme-Based Research Scheme grant T12-701/17-R to MLL. References [1] Chen, W., et al., Cancer statistics in China, 2015. CA Cancer J Clin, 2016. 66(2): p. 115-32. [2] Peng, L., et al., CCGD-ESCC: A Comprehensive Database for Genetic Variants Associated with Esophageal Squamous Cell Carcinoma in Chinese Population. Genomics Proteomics Bioinformatics, 2018. 16(4): p. 262-268. [3] Fukunishi, N., et al., Induction of DeltaNp63 by the newly identified keratinocyte-specific transforming growth factor beta Signaling Pathway with Smad2 and IkappaB Kinase alpha in squamous cell carcinoma. Neoplasia, 2010. 12(12): p. 969-79. [4] Moses, M.A., et al., Molecular Mechanisms of p63-Mediated Squamous Cancer Pathogenesis. Int J Mol Sci, 2019. 20(14).-
dc.languageeng-
dc.publisherAmerican Association for Cancer Research. The Journal's web site is located at http://cancerres.aacrjournals.org/-
dc.relation.ispartofCancer Research-
dc.relation.ispartofAmerican Association for Cancer Research (AACR) Annual Meeting-
dc.titleFunctional and mechanistic characterization of ΔNp63α in esophageal squamous cell carcinoma-
dc.typeConference_Paper-
dc.identifier.emailYu, Z: zvyu@hku.hk-
dc.identifier.emailLaw, SYK: slaw@hku.hk-
dc.identifier.emailLung, ML: mlilung@hku.hk-
dc.identifier.authorityYu, Z=rp02756-
dc.identifier.authorityLaw, SYK=rp00437-
dc.identifier.authorityLung, ML=rp00300-
dc.description.natureabstract-
dc.identifier.doi10.1158/1538-7445.AM2022-5835-
dc.identifier.hkuros333590-
dc.identifier.volume82-
dc.identifier.issue12, Suppl.-
dc.identifier.spageabstract 5835:-
dc.identifier.epageabstract 5835:-
dc.publisher.placeUnited States-

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