title: Autocrine IGF1 Signaling Mediates Pancreatic Tumor Cell Dormancy in the Absence of Oncogenic Drivers.
abstract: Mutant KRAS and c-MYC are oncogenic drivers and rational therapeutic targets for the treatment of pancreatic cancer. Although tumor growth and homeostasis are largely dependent on these oncogenes, a few residual cancer cells are able to survive the ablation of mutant KRAS and c-MYC. By performing a genome-wide gene expression analysis of in vivo-derived bulk tumor cells and residual cancer cells lacking the expression of mutant KRAS or c-MYC, we have identified an increase in autocrine IGF1/AKT signaling as a common survival mechanism in dormant cancer cells. The pharmacological inhibition of IGF-1R reduces residual disease burden and cancer recurrence, suggesting that this molecular pathway is crucial for the survival of cancer cells in the absence of the primary oncogenic drivers.
authors.affiliation: Eppley Institute for Research in Cancer and Allied Diseases, University of Nebraska Medical Center, 985950 Nebraska Medical Center, Omaha, NE 68198-5950, USA; Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center, 985950 Nebraska Medical Center, Omaha, NE 68198-5950, USA.
authors.forename: Nirakar
authors.initials: N
authors.lastname: Rajbhandari
authors.affiliation: Eppley Institute for Research in Cancer and Allied Diseases, University of Nebraska Medical Center, 985950 Nebraska Medical Center, Omaha, NE 68198-5950, USA.
authors.forename: Wan-Chi
authors.initials: WC
authors.lastname: Lin
authors.affiliation: Eppley Institute for Research in Cancer and Allied Diseases, University of Nebraska Medical Center, 985950 Nebraska Medical Center, Omaha, NE 68198-5950, USA.
authors.forename: Barbara L
authors.initials: BL
authors.lastname: Wehde
authors.affiliation: Eppley Institute for Research in Cancer and Allied Diseases, University of Nebraska Medical Center, 985950 Nebraska Medical Center, Omaha, NE 68198-5950, USA.
authors.forename: Aleata A
authors.initials: AA
authors.lastname: Triplett
authors.affiliation: Eppley Institute for Research in Cancer and Allied Diseases, University of Nebraska Medical Center, 985950 Nebraska Medical Center, Omaha, NE 68198-5950, USA; Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center, 985950 Nebraska Medical Center, Omaha, NE 68198-5950, USA; Department of Pathology and Microbiology, University of Nebraska Medical Center, 985950 Nebraska Medical Center, Omaha, NE 68198-5950, USA. Electronic address: kuwagner@unmc.edu.
authors.forename: Kay-Uwe
authors.initials: KU
authors.lastname: Wagner
mesh_terms: D000818:Animals; D019898:Autocrine Communication / Q000235:genetics*; D063646:Carcinogenesis / Q000235:genetics / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000235:genetics; D015870:Gene Expression / Q000235:genetics; D016259:Genes, myc / Q000235:genetics; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000235:genetics*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D009154:Mutation / Q000235:genetics; D009364:Neoplasm Recurrence, Local / Q000235:genetics / Q000473:pathology; D009857:Oncogenes / Q000235:genetics*; D010179:Pancreas / Q000473:pathology; D010190:Pancreatic Neoplasms / Q000235:genetics* / Q000473:pathology*; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics; D016283:Proto-Oncogene Proteins p21(ras) / Q000235:genetics; D017526:Receptor, IGF Type 1 / Q000235:genetics; D015398:Signal Transduction / Q000235:genetics*
chemical_list: D007334:Insulin-Like Growth Factor I; D017526:Receptor, IGF Type 1; D051057:Proto-Oncogene Proteins c-akt; D016283:Proto-Oncogene Proteins p21(ras)
keywords: AKT; IGF1 signaling; KRAS; c-MYC; cancer dormancy; genetic engineering; mouse models; oncogenes; pancreatic cancer