Grant: Operating Grant

Tumors of various tissue origins, such as breast, ovary or kidney occur because of mutations in very different genes. However, cancers do shares some near-universal features including the fact that the center of tumors often lacks oxygen (termed hypoxia). Our cells are programmed to produce energy exclusively from the degradation of sugar (glucose) in the absence of oxygen in a process that is called fermentation or anaerobic metabolism. Yeasts produce alcohol when they ferment glucose in the absence of oxygen. In the case of higher organisms, like humans, we produce lactic acid. Therefore, the middle of tumors is often very acidic compared to normal tissues. It is generally agreed upon that tumors that are hypoxic and acidic are likely to be more aggressive. That is because cells in the middle of the tumors have been able to survive this particularly harsh environment whereas cells that did not are already dead. My laboratory is interested in the study of this process of cellular adaptation to anaerobic metabolism. Our group has published papers that demonstrate that cells that engage in anaerobic metabolism are able to store or hide several proteins in a cellular closet (i.e. nucleolus) because they do not need them, or want them, in the absence of oxygen. We also showed that when we prevent this hiding of proteins, cells cannot survive anaerobic metabolism an die. This proposal is to continue studying this process in the idea of preventing the aggressive cancer cells to survive in the core of tumors as a way to treat cancer.