Mitochondrial reactive oxygen species and cancer

By Lucas B. Sullivan, Navdeep S. Chandel. Cancer & Metabolism, 2014

732 citations recorded by the source corpus.

Mitochondria produce reactive oxygen species (mROS) as a natural by-product of electron transport chain activity. While initial studies focused on the damaging effects of reactive oxygen species, a recent paradigm shift has shown that mROS can act as signaling molecules to activate pro-growth responses. Cancer cells have long been observed to have increased production of ROS relative to normal cells, although the implications of this increase were not always clear. This is especially interesting considering cancer cells often also induce expression of antioxidant proteins. Here, we discuss how cancer-associated mutations and microenvironments can increase production of mROS, which can lead to activation of tumorigenic signaling and metabolic reprogramming. This tumorigenic signaling also increases expression of antioxidant proteins to balance the high production of ROS to maintain redox homeostasis. We also discuss how cancer-specific modifications to ROS and antioxidants may be targeted for therapy.

Subfields: Cancer Research, Molecular Biology

View Paper: https://www.semanticscholar.org/paper/2bfad2bd008f9d6b30b849272d70ed978c799f11

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Cancer Research

1. W. Zong
2. M. Santoro
3. Joshua D. Rabinowitz
4. E. White
5. Alec C. Kimmelman
6. C. Lyssiotis
7. E. Panieri

In Molecular Biology

1. Alec C. Kimmelman
2. E. White
3. W. Zong
4. M. Santoro
5. Joshua D. Rabinowitz
6. C. Lyssiotis
7. E. Panieri
8. Guido Kroemer

Citations in the corpus

• Superoxide dismutases: Dual roles in controlling ROS damage and regulating ROS signaling (2018, unknown): “For example, activation of the PI3K/AKT signaling transduction pathway, one of the major targets of ROS, can promote proliferation, metabolic adaption, and cell mobility (Cantley, 2002; Leslie et al., 2003; Pelicano et al., 2006; Sullivan and Chandel, 2014).”
• ROS homeostasis and metabolism: a dangerous liason in cancer cells (2016, background): “By regulating the generation of ROS, ATP and other metabolites driving bioenergetic and biosynthetic processes, mitochondria have a key role in cancer progression.(132,133) Oncogenic activation of MYC and KRAS promote increased glucose utilization and addiction in different types of tumors,(134) whi”
• Mitochondria and Cancer (2016, background): “The reactive oxygen species (ROS) generated in mitochondria as a byproduct of the ETC can activate signal transduction pathways such as that of MAP kinase and the HIFs (in normoxia is referred to as pseudohypoxia) (Shadel and Horvath, 2015; Sullivan and Chandel, 2014).”
• PGC-1α, Inflammation, and Oxidative Stress: An Integrative View in Metabolism (2020, background): “act as signaling molecules to activate pro-growth responses linked with several essential cellular signaling processes of growth regulation, differentiation, proliferation, and apoptosis [75, 76].”
• Calcium and ROS: A mutual interplay (2015, background): “Newer evidence suggests that mitochondrial ROS can also act as signaling molecules to activate pro-growth responses [139].”
• Metabolic Interactions in the Tumor Microenvironment (2017, background): “Given that cancer cells are often under intense redox stress, particularly when exposed to chemotherapies, there is increased demand for cysteine [74].”