Data from Glucose Metabolism Reprogrammed by Overexpression of IKKϵ Promotes Pancreatic Tumor Growth
Year: 2023
Type: other
Abstract: 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.
Authors: 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
Language: English
Subfield: Cancer Research
Domain: Life Sciences
Open Access status: gold
OpenAlex ID: W4361237953