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You searched for +publisher:"University of North Carolina" +contributor:("Bang, Deepali"). One record found.

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University of North Carolina

1. Bang, Deepali. Oncogenic KRAS, GSK-3, NF-κB and TBK1: the interplay and consequences in promoting pancreatic and lung cancer.

Degree: Cell Biology and Physiology, 2014, University of North Carolina

The development of KRAS targeted therapy has evolved into targeting the complex signaling pathways activated downstream of oncogenic KRAS and associated with disease progression. Recent focus has been made on targeting the constitutive activation of the transcription factor, NF-κB. However, advancement of this therapeutic strategy is dependent on fully understanding the elusive mechanisms underlying constitutive NF-κB activity in KRAS driven cancers. Glycogen synthase kinase-3 has previously been implicated in regulating pro-survival NF-κB signaling in pancreatic cancer cells through IκB kinase (IKK), but a distinction between roles of the individual isoforms, GSK-3α and GSK-β has not been done. Moreover, TGF-β activated kinase 1 (TAK1), an upstream regulator of IKK activity, was recently shown to regulate survival in KRAS positive colorectal cancers. Here, we characterize mutant KRAS dependent GSK-3α regulation of NF-κB in pancreatic cancer cells. Our data suggests that mutant KRAS upregulates GSK-3α, which promotes pro-survival canonical NF-κB via stabilization of TAK-TAB complex. We also provide initial evidence of GSK-3α dependent regulation of pro-survival non-canonical NF-κB in pancreatic cancer cells. Importantly, we show that pharmacological inhibition of GSK-3 suppresses growth of human pancreatic tumor explants with a concomitant loss of oncogenic gene expression like c-MYC and TERT. Collectively, we propose that GSK-3α regulates multiple arms of NF-κB pathway in KRAS positive pancreatic cancer cells, identifying GSK-3α as promising therapeutic target. Recently, Tank Binding Kinase-1 (TBK1), an IKK-related kinase, has been implicated in survival of KRAS positive cancer cells. Here, we use a conditional TBK1 knockout mouse model with simultaneous activation of KRAS and inactivation of p53 in lung epithelial cells to provide initial evidence of a role of TBK1 in KRAS driven lung tumorigenesis. These data broadens our understanding of NF-κB regulation in KRAS malignancies and implicates GSK-3α, TAK1 and TBK1 as emerging therapeutic targets. Advisors/Committee Members: Bang, Deepali, Baldwin, Albert.

Subjects/Keywords: School of Medicine; Department of Cell Biology and Physiology

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6th Edition):

Bang, D. (2014). Oncogenic KRAS, GSK-3, NF-κB and TBK1: the interplay and consequences in promoting pancreatic and lung cancer. (Thesis). University of North Carolina. Retrieved from https://cdr.lib.unc.edu/record/uuid:44cd018a-4603-47ca-9d75-5478a07d041d

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16th Edition):

Bang, Deepali. “Oncogenic KRAS, GSK-3, NF-κB and TBK1: the interplay and consequences in promoting pancreatic and lung cancer.” 2014. Thesis, University of North Carolina. Accessed September 27, 2020. https://cdr.lib.unc.edu/record/uuid:44cd018a-4603-47ca-9d75-5478a07d041d.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7th Edition):

Bang, Deepali. “Oncogenic KRAS, GSK-3, NF-κB and TBK1: the interplay and consequences in promoting pancreatic and lung cancer.” 2014. Web. 27 Sep 2020.

Vancouver:

Bang D. Oncogenic KRAS, GSK-3, NF-κB and TBK1: the interplay and consequences in promoting pancreatic and lung cancer. [Internet] [Thesis]. University of North Carolina; 2014. [cited 2020 Sep 27]. Available from: https://cdr.lib.unc.edu/record/uuid:44cd018a-4603-47ca-9d75-5478a07d041d.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Bang D. Oncogenic KRAS, GSK-3, NF-κB and TBK1: the interplay and consequences in promoting pancreatic and lung cancer. [Thesis]. University of North Carolina; 2014. Available from: https://cdr.lib.unc.edu/record/uuid:44cd018a-4603-47ca-9d75-5478a07d041d

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

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