Metabolic and bioenergetic alterations in cancer cells. Coordinator: Fato

Research themes

Cancer is a disease that induces profound genetic, bioenergetics and histological differences in comparison to non-transformed cells. Cancer cells are characterized by modifications associated with unlimited cell growth, inhibition of apoptosis and intense anabolism. The metabolic reprogramming is a crucial step into the transformation from a normal to a malignant cancer cell. The more common metabolic remodeling described in tumor cells is an increased glucose uptake, a higher aerobic glycolytic capacity associated to a high lactate production, along with a decreased rate of oxygen consumption by the mitochondrial respiratory chain despite of high oxygen concentration (Warburg effect). To explain these abnormal bioenergetics phenotype, pioneering hypotheses proposed the impairment of mitochondrial function in rapidly growing cancer cells. Nevertheless, there are many studies showing that mitochondria in tumor cells are not inactive per se but operate at low capacity. So that cancer cells, in spite of possessing functional mitochondria, can switch between glycolytic and oxidative metabolism in a reversible fashion (the Crabtree effect). The specific advantages of this metabolic switch are unknown, although it is possible that this mechanism could favor the cell proliferation in hypoxic environments, conditions normally observed in solid tumors. Another explanation is that the down-regulation of oxidative metabolism could help these cells to escape from apoptotic cell death. Another characteristic of tumor cells is invasiveness, closely related to the malignancy of the tumor and its ability to give metastases. Some authors have highlighted the relationship between the glycolytic metabolic phenotype and tumor invasiveness.

The group's research activity is divided into three main lines:

1. Redox signaling in cancer: membrane NAD(P)H oxidases (Nox), aquaporins, glucose transport and their implication in signal transduction processes.
2. Lipid metabolism in cancer: study of the role of lipids, and in particular of a new class of hydroxylated fatty acids and their corresponding esters (FAHFAs) in the metabolic reprogramming of cancer cells.
3. Bioenergetics in cancer: study of the role of mitochondria in tumor proliferation with particular attention to the study of the relationship between oxidative and glycolytic metabolism in the adaptive capacity of tumor cells to nutrient deficiency.

Lab Members

Research Line 1: Cecilia Prata (Associate Professor); Diana Fiorentini (Researcher)

Reserch Line 2:  Natalia Calonghi (Associate Professor)

Research Line 3: Romana Fato (Associate Professor); Christian Bergamini (Associate Professor); Nicola Rizzardi (PhD Student); Francesca Valenti (PhD Student).

Laura Zambonin, Technician.

Internship Projects 

Research line 1: one internship position each year

Research line 2: two internship positions each year

Research line 3: three internship positions each year

Main publications

- Liparulo, I.; Bergamini, C.; Bortolus, M.; Calonghi, N.; Gasparre, G.; Kurelac, I.; Masin, L.; Rizzardi, N.; Rugolo, M.; Wang, W.; Aleo, S.J.; Kiwan, A. “Coenzyme Q biosynthesis inhibition induces HIF-1α stabilization and metabolic switch toward glycolysis” FEBS Journal Volume 288, Issue 6, Pages 1956 – 1974 March 2021; https://doi.org/10.1111/febs.15561

- Wang W.; Liparulo I.; Rizzardi N.; Bolignano P.; Calonghi N.; Bergamini C. and Fato R. “Coenzyme Q Depletion Reshapes MCF-7 Cells Metabolism” Int. J. Mol. Sci. 2021, 22(1), 198; https://doi.org/10.3390/ijms22010198

- Albadri, S.; Naso, F.; Thauvin, M.; Gauron, C.; Parolin, C.; Duroure, K.; Vougny, J.; Fiori, J.; Boga, C.; Vriz, S.; Calonghi, N.; Del Bene, F. “Redox Signaling via Lipid Peroxidation Regulates Retinal Progenitor Cell Differentiation” Developmental Cell Open Access Volume 50, Issue 1, Pages 73 - 89.e61 July 2019; https://doi.org/10.1016/j.devcel.2019.05.011

- Rizzardi, N.; Pezzolesi, L.; Samorì, C.; Senese, F.; Zalambani, C.; Pitacco, W.; Calonghi, N.; Bergamini, C. “Natural Astaxanthin Is a Green Antioxidant Able to Counteract Lipid Peroxidation and Ferroptotic Cell Death” International Journal of Molecular Sciences Open Access Volume 23, Issue 23December 2022; https://doi.org/10.3390/ijms232315137

- Prata C.; Facchini C.; Leoncini E.; Lenzi M.; Maraldi T.; Angeloni C.; Zambonin L.; Hrelia S.; Fiorentini D. “Sulforaphane Modulates AQP8-Linked Redox Signalling in Leukemia Cells” Oxidative Medicine and Cellular Longevity, Open Access Nov 18; 2018:4125297, 2018; https://doi.org/10.1155/2018/4125297