American Association for Cancer Research
10780432ccr121789-sup-tab4.xlsx (11.61 kB)

Supplementary Table 4 from Overexpression of Ecdysoneless in Pancreatic Cancer and Its Role in Oncogenesis by Regulating Glycolysis

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posted on 2023-03-31, 17:11 authored by Parama Dey, Satyanarayana Rachagani, Subhankar Chakraborty, Pankaj K. Singh, Xiangshan Zhao, Channabasavaiah Basavaraju Gurumurthy, Judy M. Anderson, Subodh Lele, Michael A. Hollingsworth, Vimla Band, Surinder K. Batra

XLSX file - 11K, Expression of Ecd in metastasis from Ecd positive vs. negative pancreatic tumors



Purpose: To study the expression and function of a novel cell-cycle regulatory protein, human ecdysoneless (Ecd), during pancreatic cancer pathogenesis.Experimental Design: Immunohistochemical expression profiling of Ecd was done in nonneoplastic normal pancreatic tissues and pancreatic ductal adenocarcinoma lesions (from tissue microarray and Rapid Autopsy program) as well as precancerous PanIN lesions and metastatic organs. To analyze the biological significance of Ecd in pancreatic cancer progression, Ecd was stably knocked down in pancreatic cancer cell line followed by in vitro and in vivo functional assays.Results: Normal pancreatic ducts showed very weak to no Ecd expression compared to significant positive expression in pancreatic cancer tissues (mean ± SE composite score: 0.3 ± 0.2 and 3.8 ± 0.2 respectively, P < 0.0001) as well as in PanIN precursor lesions with a progressive increase in Ecd expression with increasing dysplasia (PanIN-1–PanIN-3). Analysis of matched primary tumors and metastases from patients with pancreatic cancer revealed that Ecd is highly expressed in both primary pancreatic tumor and in distant metastatic sites. Furthermore, knockdown of Ecd suppressed cell proliferation in vitro and tumorigenicity of pancreatic cancer cells in mice orthotopic tumors. Microarray study revealed that Ecd regulates expression of glucose transporter GLUT4 in pancreatic cancer cells and was subsequently shown to modulate glucose uptake, lactate production, and ATP generation by pancreatic cancer cells. Finally, knockdown of Ecd also reduced level of pAkt, key signaling molecule known to regulate aerobic glycolysis in cancer cells.Conclusion: Ecd is a novel tumor-promoting factor that is differentially expressed in pancreatic cancer and potentially regulates glucose metabolism within cancer cells. Clin Cancer Res; 18(22); 6188–98. ©2012 AACR.

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