The Warburg Effect: How Does it Benefit Cancer Cells?

Abstract

Cancer cells rewire their metabolism to promote growth, survival, proliferation, and long-term maintenance. The common feature of this altered metabolism is the increased glucose uptake and fermentation of glucose to lactate. This phenomenon is observed even in the presence of completely functioning mitochondria and, together, is known as the 'Warburg Effect'. The Warburg Effect has been documented for over 90 years and extensively studied over the past 10 years, with thousands of papers reporting to have established either its causes or its functions. Despite this intense interest, the function of the Warburg Effect remains unclear. Here, we analyze several proposed explanations for the function of Warburg Effect, emphasize their rationale, and discuss their controversies.

Keywords: ATP synthesis; ROS; Warburg Effect; chromatin remodeling; microenvironment acidification.

Figure 1. The frequency of publications on the Warburg Effect from the 1920s-2010s

The Warburg Effect has been studied extensively since the 1920s with a surge in the number of publications from the 2000s to today. Many of the proposed functions of the Warburg Effect have also gained vastly renewed interest. Although energy (ATP), biosynthesis, and ROS have been intricately studied in the context of the Warburg Effect, acidification and acetylation have only recently gained attention.

Figure 2. Summary of the proposed functions of the Warburg Effect

The Warburg Effect is defined as an increase in the rate of glucose uptake and preferential production of lactate, even in the presence of oxygen. Each of these functions have been hypothesized to be the function of the Warburg Effect.