American Association for Cancer Research
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Supplementary Figures S1-S7 from Glucose Metabolism Reprogrammed by Overexpression of IKKϵ Promotes Pancreatic Tumor Growth

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journal contribution
posted on 2023-03-31, 00:20 authored by Haseeb Zubair, Shafquat Azim, Sanjeev Kumar Srivastava, Aamir Ahmad, Arun Bhardwaj, Mohammad Aslam Khan, Girijesh Kumar Patel, Sumit Arora, James Elliot Carter, Seema Singh, Ajay Pratap Singh

IKKepsilon expression in pancreatic tumor samples and PDAC cell lines (S1); Ectopic expression of IKKepsilon enhances growth of pancreatic cancer cells (S2); Transient knockdown of IKKepsilon in MiaPaCa and Colo357 cells by siRNA (S3); Forced expression of IKKepsilon in BxPC3 cells enhances glucose-uptake and consumption (S4); Overexpression of IKKepsilon in BxPC3 enhanced the expression and nuclear translocation of c-MYC (S5); IKKepsilon knockdown decreases half-life of c-MYC in MiaPaCa and Colo357 cells (S6); Ectopic expression of IKKepsilon in pancreatic cancer cell line BxPC3 activates Akt (S7).



the University of South Alabama Mitchell Cancer Institute



Aberrant expression of the kinase IKKϵ in pancreatic ductal adenocarcinoma (PDAC) has been associated with poor prognosis. In this study, we define a pathobiologic function for IKKϵ in reprogramming glucose metabolism and driving progression in PDAC. Silencing IKKϵ in PDAC cells, which overexpressed it endogenously, was sufficient to reduce malignant cell growth, clonogenic potential, glucose consumption, lactate secretion, and expression of genes involved in glucose metabolism, without impacting the basal oxygen consumption rate. IKKϵ silencing also attenuated c-Myc in a manner associated with diminished signaling through an AKT/GSK3β/c-MYC phosphorylation cascade that promoted MYC nuclear accumulation. In an orthotopic mouse model, IKKϵ-silenced PDAC exhibited a relative reduction in glucose uptake, tumorigenicity, and metastasis. Overall, our findings offer a preclinical mechanistic rationale to target IKKϵ to improve the therapeutic management of PDAC in patients. Cancer Res; 76(24); 7254–64. ©2016 AACR.

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