Abstract Esophageal 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). Citation Format: Shan Shan So, Valen Z. Yu, Simon Y. Law, Maria L. Lung. Functional and mechanistic characterization of ΔNp63α in esophageal squamous cell carcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 5835.
With the introduction of safe, effective nonoperative alternatives, bypass surgery for unresectable esophageal cancer is infrequently performed, but it has a limited role in palliation of esophageal cancer that needs to be defined.Retrospective cohort study.Department of Surgery at Queen Mary Hospital in Hong Kong.Patients who had unresectable esophageal cancer and underwent bypass surgery between January 1, 1991, and December 31, 1998.Bypass procedures were performed using a gastric or colonic conduit to the neck.Morbidity and mortality and quality of palliation.Thirty-eight patients underwent retrosternal bypass to the neck using a gastric (n = 27) or colonic (n = 11) conduit. Ten patients (26%) underwent unplanned bypass at the time of exploration for resection because of unexpected findings of T4 disease (n = 2) or technical difficulties in addition to advanced disease (n = 8). Between 1991 and 1994, 1 of 26 bypasses was unplanned and the hospital mortality was 42% (11/26), while between 1995 and 1998, 9 of 12 bypasses were unplanned and the hospital mortality was 8% (1/12). There were 12 hospital deaths in the planned bypass group (n = 28) and none in the unplanned bypass (n = 10) group (43% vs 0%, P =.01). The median survival in patients who underwent unplanned bypass was 6.9 months, compared with 1.9 months in patients who underwent planned bypass (P =.004). All patients were discharged from the hospital on at least a semisolid diet.The Kirschner operation is largely obsolete as a planned procedure because of high morbidity and mortality. Bypass surgery, however, is a reasonable option as an unplanned procedure when resection is precluded at the time of exploration because of unexpected adverse operative findings.
<p>Quantification of number of cells that migrated through a membrane, invaded through a Matrigel-coated membrane, formed spheroids or formed colonies in (A) KYSE150-Luc cells co-cultured with conditioned medium collected from EV or FSTL1 OE cells; or (B) KYSE150-Luc cells treated with control or recombinant FSTL1, in the presence or absence of IMD-0354.</p>
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