Stress-induced cleavage of Myc promotes cancer cell survival

Conacci-Sorrell M, Ngouenet C, Anderson S, Brabletz T, Eisenman RN (2014)

Publication Type: Journal article

Publication year: 2014

Journal

Genes & Development Cold Spring Harbor Laboratory Press

Publisher: Cold Spring Harbor Laboratory Press

Book Volume: 28

Pages Range: 689-707

Journal Issue: 7

DOI: 10.1101/gad.231894.113

Abstract

Evasion of apoptosis is critical in Myc-induced tumor progression. Here we report that cancer cells evade death under stress by activating calpain-mediated proteolysis of Myc. This generates Myc-nick, a cytoplasmic, transcriptionally inactive cleavage product of Myc. We found conversion of Myc into Myc-nick in cell lines and tissues derived from multiple cancers. In colon cancer, the production of Myc-nick is enhanced under stress conditions such as hypoxia and nutrient deprivation. Under these conditions, ectopic expression of Myc-nick promotes anchorage-independent growth and cell survival at least in part by promoting autophagy. Myc-nick also delays colon cancer cell death after treatment with chemotherapeutic drugs such as etoposide, cisplatin, and imatinib. Furthermore, colon cancer cells expressing a cleavage-resistant form of Myc undergo extensive apoptosis but are rescued by overexpression of Myc-nick. We also found that ectopic expression of Myc-nick results in the induction of the actin-bundling protein fascin, formation of filopodia, and increased cell motility-all mediators of tumor metastasis. Myc-nick-induced survival, autophagy, and motility require Myc box II (MBII), a region of Myc-nick that recruits acetyltransferases that in turn modify cytoplasmic proteins, including ?-tubulin and ATG3. Our results suggest that Myc-nick-induced survival and motility contribute to colon cancer progression and metastasis.

Authors with CRIS profile

Thomas Brabletz Lehrstuhl für Experimentelle Medizin mit dem Schwerpunkt Molekulare Pathogeneseforschung

Involved external institutions

Fred Hutchinson Cancer Research Center US United States (USA) (US)

How to cite

APA:

Conacci-Sorrell, M., Ngouenet, C., Anderson, S., Brabletz, T., & Eisenman, R.N. (2014). Stress-induced cleavage of Myc promotes cancer cell survival. Genes & Development, 28(7), 689-707. https://doi.org/10.1101/gad.231894.113

MLA:

Conacci-Sorrell, Maralice, et al. "Stress-induced cleavage of Myc promotes cancer cell survival." Genes & Development 28.7 (2014): 689-707.

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