Reversible Myc hypomorphism identifies a key Myc-dependency in early cancer evolution

Nicole M. Sodir (), Luca Pellegrinet, Roderik M. Kortlever, Tania Campos, Yong-Won Kwon, Shinseog Kim, Daniel Garcia, Alessandra Perfetto, Panayiotis Anastasiou, Lamorna Brown Swigart, Mark J. Arends, Trevor D. Littlewood and Gerard I. Evan ()
Additional contact information
Nicole M. Sodir: University of Cambridge
Luca Pellegrinet: University of Cambridge
Roderik M. Kortlever: University of Cambridge
Tania Campos: University of Cambridge
Yong-Won Kwon: Abcam, 860 Auburn Ct
Shinseog Kim: Center for Genomic Integrity, Institute for Basic Science
Daniel Garcia: Oncogenesis Thematic Research Center at Bristol Myers Squibb
Alessandra Perfetto: University of Cambridge
Panayiotis Anastasiou: University of Cambridge
Lamorna Brown Swigart: University of California
Mark J. Arends: University of Edinburgh
Trevor D. Littlewood: University of Cambridge
Gerard I. Evan: University of Cambridge

Nature Communications, 2022, vol. 13, issue 1, 1-14

Abstract: Abstract Germ-line hypomorphism of the pleiotropic transcription factor Myc in mice, either through Myc gene haploinsufficiency or deletion of Myc enhancers, delays onset of various cancers while mice remain viable and exhibit only relatively mild pathologies. Using a genetically engineered mouse model in which Myc expression may be systemically and reversibly hypomorphed at will, we asked whether this resistance to tumour progression is also emplaced when Myc hypomorphism is acutely imposed in adult mice. Indeed, adult Myc hypomorphism profoundly blocked KRasG12D-driven lung and pancreatic cancers, arresting their evolution at the early transition from indolent pre-tumour to invasive cancer. We show that such arrest is due to the incapacity of hypomorphic levels of Myc to drive release of signals that instruct the microenvironmental remodelling necessary to support invasive cancer. The cancer protection afforded by long-term adult imposition of Myc hypomorphism is accompanied by only mild collateral side effects, principally in haematopoiesis, but even these are circumvented if Myc hypomorphism is imposed metronomically whereas potent cancer protection is retained.

Date: 2022
References: View references in EconPapers View complete reference list from CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-022-34079-x Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-34079-x

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-022-34079-x

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().