title: Endogenous Myc maintains the tumor microenvironment.
abstract: The ubiquitous deregulation of Myc in human cancers makes it an intriguing therapeutic target, a notion supported by recent studies in Ras-driven lung tumors showing that inhibiting endogenous Myc triggers ubiquitous tumor regression. However, neither the therapeutic mechanism nor the applicability of Myc inhibition to other tumor types driven by other oncogenic mechanisms is established. Here, we show that inhibition of endogenous Myc also triggers ubiquitous regression of tumors in a simian virus 40 (SV40)-driven pancreatic islet tumor model. Such regression is presaged by collapse of the tumor microenvironment and involution of tumor vasculature. Hence, in addition to its diverse intracellular roles, endogenous Myc serves an essential and nonredundant role in coupling diverse intracellular oncogenic pathways to the tumor microenvironment, further bolstering its credentials as a pharmacological target.
authors.affiliation: Department of Pathology, University of California at San Francisco, San Francisco, California 94143, USA.
authors.forename: Nicole M
authors.initials: NM
authors.lastname: Sodir
authors.forename: Lamorna Brown
authors.initials: LB
authors.lastname: Swigart
authors.forename: Anthony N
authors.initials: AN
authors.lastname: Karnezis
authors.forename: Douglas
authors.initials: D
authors.lastname: Hanahan
authors.forename: Gerard I
authors.initials: GI
authors.lastname: Evan
authors.forename: Laura
authors.initials: L
authors.lastname: Soucek
mesh_terms: D007516:Adenoma, Islet Cell; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis / Q000502:physiology; D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D004195:Disease Models, Animal; D004318:Doxycycline / Q000494:pharmacology; D020690:GTPase-Activating Proteins / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D051379:Mice; D018358:Neuroendocrine Tumors / Q000098:blood supply / Q000473:pathology / Q000503:physiopathology; D011485:Protein Binding; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics / Q000378:metabolism*; D012097:Repressor Proteins / Q000378:metabolism; D013539:Simian virus 40 / Q000502:physiology; D059016:Tumor Microenvironment / Q000502:physiology*
chemical_list: D000970:Antineoplastic Agents; D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; D020690:GTPase-Activating Proteins; C484561:Mnt protein, mouse; D016271:Proto-Oncogene Proteins c-myc; C490620:Ralbp1 protein, mouse; D012097:Repressor Proteins; D004318:Doxycycline