Essential roles of Caspase-3 in facilitating Myc-induced genetic instability and carcinogenesis.

Published online

Journal Article

The mechanism for Myc-induced genetic instability is not well understood. Here we show that sublethal activation of Caspase-3 plays an essential, facilitative role in Myc-induced genomic instability and oncogenic transformation. Overexpression of Myc resulted in increased numbers of chromosome aberrations and γH2AX foci in non-transformed MCF10A human mammary epithelial cells. However, such increases were almost completely eliminated in isogenic cells with CASP3 gene ablation. Furthermore, we show that endonuclease G, an apoptotic nuclease downstream of Caspase-3, is directly responsible for Myc-induced genetic instability. Genetic ablation of either CASP3 or ENDOG prevented Myc-induced oncogenic transformation of MCF10A cells. Taken together, we believe that Caspase-3 plays a critical, unexpected role in mediating Myc-induced genetic instability and transformation in mammalian cells.

Full Text

Duke Authors

Cited Authors

  • Cartwright, IM; Liu, X; Zhou, M; Li, F; Li, C-Y

Published Date

  • July 10, 2017

Published In

Volume / Issue

  • 6 /

PubMed ID

  • 28691902

Pubmed Central ID

  • 28691902

Electronic International Standard Serial Number (EISSN)

  • 2050-084X

Digital Object Identifier (DOI)

  • 10.7554/eLife.26371

Language

  • eng

Conference Location

  • England