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Article Addendum

Role of Autophagy in Breast Cancer

Vassiliki Karantza-Wadsworth and Eileen White

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Autophagy is an evolutionarily conserved process of cytoplasm and cellular organelle degradation in lysosomes. Autophagy is a survival pathway required for cellular viability during starvation; however, if it proceeds to completion, autophagy can lead to cell death. In neurons, constitutive autophagy limits accumulation of polyubiquitinated proteins and prevents neuronal degeneration. Therefore, autophagy has emerged as a homeostatic mechanism regulating the turnover of long-lived or damaged proteins and organelles, and buffering metabolic stress under conditions of nutrient deprivation by recycling intracellular constituents. Autophagy also plays a role in tumorigenesis, as the essential autophagy regulator beclin1 is monoallelically deleted in many human ovarian, breast, and prostate cancers, and beclin1^+/- mice are tumor-prone. We found that allelic loss of beclin1 renders immortalized mouse mammary epithelial cells susceptible to metabolic stress and accelerates lumen formation in mammary acini. Autophagy defects also activate the DNA damage response in vitro and in mammary tumors in vivo, promote gene amplification, and synergize with defective apoptosis to accelerate mammary tumorigenesis. Thus, loss of the prosurvival role of autophagy likely contributes to breast cancer progression by promoting genome damage and instability. Exploring the yet unknown relationship between defective autophagy and other breast cancer-promoting functions may provide valuable insight into the pathogenesis of breast cancer and may have significant prognostic and therapeutic implications for breast cancer patients.

Addendum to:
Autophagy Mitigates Metabolic Stress and Genome Damage in Mammary Tumorigenesis
V. Karantza-Wadsworth, S. Patel, O. Kravchuk, G. Chen, R. Mathew, S. Jin and E. White
Genes Dev 2007; 21:1621-35

Authors

Vassiliki Karantza-Wadsworth

Division of Medical Oncology; Department of Medicine; University of Medicine and Dentistry of New Jersey; Robert Wood Johnson Medical School; Piscataway, New Jersey USA; The Cancer Institute of New Jersey; New Brunswick, New Jersey USA

Eileen White

Rutgers University

This is an open-access article

 Download PDF

If the document does not open, please right-click on the link (control-click on a Macintosh) and select the option to save the file to disk.