Front. Oncol., 21 November 2012 |

The interplay between autophagy and ROS in tumorigenesis

  • 1Robert Wood Johnson Medical School, University of Medicine and Dentistry of New Jersey, Piscataway NJ, USA
  • 2The Cancer Institute of New Jersey, New Brunswick, NJ, USA
  • 3Division of Medical Oncology, Department of Internal Medicine, Robert Wood Johnson Medical School, University of Medicine and Dentistry of New Jersey, Piscataway, NJ, USA

Reactive oxygen species (ROS) at physiological levels are important cell signaling molecules. However, aberrantly high ROS are intimately associated with disease and commonly observed in cancer. Mitochondria are primary sources of intracellular ROS, and their maintenance is essential to cellular health. Autophagy, an evolutionarily conserved process whereby cytoplasmic components are delivered to lysosomes for degradation, is responsible for mitochondrial turnover and removal of damaged mitochondria. Impaired autophagy is implicated in many pathological conditions, including neurological disorders, inflammatory bowel disease, diabetes, aging, and cancer. The first reports connecting autophagy to cancer showed that allelic loss of the essential autophagy gene BECLIN1 (BECN1) is prevalent in human breast, ovarian, and prostate cancers and that Becn1+/- mice develop mammary gland hyperplasias, lymphomas, lung and liver tumors. Subsequent studies demonstrated that Atg5-/- and Atg7-/- livers give rise to adenomas, Atg4C-/- mice are susceptible to chemical carcinogenesis, and Bif1-/- mice are prone to spontaneous tumors, indicating that autophagy defects promote tumorigenesis. Due to defective mitophagy, autophagy-deficient cells accumulate damaged mitochondria and deregulated ROS levels, which likely contribute to their tumor-initiating capacity. However, the role of autophagy in tumorigenesis is complex, as more recent work also revealed tumor dependence on autophagy: autophagy-competent mutant-Ras-expressing cells form tumors more efficiently than their autophagy-deficient counterparts; similarly, FIP200 deficiency suppresses PyMT-driven mammary tumorigenesis. These latter findings are attributed to the fact that tumors driven by powerful oncogenes have high metabolic demands catered to by autophagy. In this review, we discuss the relationship between ROS and autophagy and summarize our current knowledge on their functional interactions in tumorigenesis.

Keywords: autophagy, ROS, oxidative stress, cancer, p62, inflammation

Citation: Kongara S and Karantza V (2012) The interplay between autophagy and ROS in tumorigenesis. Front. Oncol. 2:171. doi: 10.3389/fonc.2012.00171

Received: 23 August 2012; Accepted: 30 October 2012;
Published online: 21 November 2012.

Edited by:

Carola A. Neumann, Medical University of South Carolina, USA

Reviewed by:

Daniel C. Hoessli, International Center for Chemical and Biological Sciences, Switzerland
Catherine Brenner, Institut National de la Santé et de la Recherche Médicale - University of Paris Sud, France

Copyright: © 2012 Kongara and Karantza. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in other forums, provided the original authors and source are credited and subject to any copyright notices concerning any third-party graphics etc.

*Correspondence: Vassiliki Karantza, The Cancer Institute of New Jersey, 195 Little Albany Street, Room 3550, New Brunswick, NJ 08903, USA.