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

Publication ,  Journal Article
Cartwright, IM; Liu, X; Zhou, M; Li, F; Li, C-Y
Published in: Elife
July 10, 2017

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.

Duke Scholars

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Published In

Elife

DOI

EISSN

2050-084X

Publication Date

July 10, 2017

Volume

6

Location

England

Related Subject Headings

  • Proto-Oncogene Proteins c-myc
  • Humans
  • Genomic Instability
  • Epithelial Cells
  • Cell Transformation, Neoplastic
  • Cell Line
  • Caspase 3
  • Carcinogenesis
  • 42 Health sciences
  • 32 Biomedical and clinical sciences
 

Citation

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Cartwright, I. M., Liu, X., Zhou, M., Li, F., & Li, C.-Y. (2017). Essential roles of Caspase-3 in facilitating Myc-induced genetic instability and carcinogenesis. Elife, 6. https://doi.org/10.7554/eLife.26371
Cartwright, Ian M., Xinjian Liu, Min Zhou, Fang Li, and Chuan-Yuan Li. “Essential roles of Caspase-3 in facilitating Myc-induced genetic instability and carcinogenesis.Elife 6 (July 10, 2017). https://doi.org/10.7554/eLife.26371.
Cartwright IM, Liu X, Zhou M, Li F, Li C-Y. Essential roles of Caspase-3 in facilitating Myc-induced genetic instability and carcinogenesis. Elife. 2017 Jul 10;6.
Cartwright, Ian M., et al. “Essential roles of Caspase-3 in facilitating Myc-induced genetic instability and carcinogenesis.Elife, vol. 6, July 2017. Pubmed, doi:10.7554/eLife.26371.
Cartwright IM, Liu X, Zhou M, Li F, Li C-Y. Essential roles of Caspase-3 in facilitating Myc-induced genetic instability and carcinogenesis. Elife. 2017 Jul 10;6.

Published In

Elife

DOI

EISSN

2050-084X

Publication Date

July 10, 2017

Volume

6

Location

England

Related Subject Headings

  • Proto-Oncogene Proteins c-myc
  • Humans
  • Genomic Instability
  • Epithelial Cells
  • Cell Transformation, Neoplastic
  • Cell Line
  • Caspase 3
  • Carcinogenesis
  • 42 Health sciences
  • 32 Biomedical and clinical sciences