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

Romana Fato, Associate Professor

Christian Bergamini, Associate Professor

Natalia Calonghi, Associate Professor

Cecilia Prata, Associate Professor

Nicola Rizzardi, PhD Student

Francesca Valenti, PhD Student

Luca Pincigher, PhD Student

Chiara Zalambani, PhD Student

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

• Diquigiovanni C, Rizzardi N, Kampmeier A, Liparulo I, Bianco F, De Nicolo B, Cataldi-Stagetti E, Cuna E, Severi G, Seri M, Bertrand M, Haack TB, Marina AD, Braun F, Fato R, Kuechler A, Bergamini C, Bonora E. “Mutant SPART causes defects in mitochondrial protein import and bioenergetics reversed by Coenzyme Q.” Open Biol. 2023 Jul;13(7):230040. doi: 10.1098/rsob.230040. Epub 2023 Jul 12. PMID: 37433330 Free PMC article.
• Bergamini C, Leoni I, Rizzardi N, Melli M, Galvani G, Coada CA, Giovannini C, Monti E, Liparulo I, Valenti F, Ferracin M, Ravaioli M, Cescon M, Vasuri F, Piscaglia F, Negrini M, Stefanelli C, Fato R, Gramantieri L, Fornari F. “MiR-494 induces metabolic changes through G6pc targeting and modulates sorafenib response in hepatocellular carcinoma.” J Exp Clin Cancer Res. 2023 Jun 10;42(1):145. doi: 10.1186/s13046-023-02718-w. PMID: 37301960
• 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
• Luca Pincigher , Francesca Valenti, Christian Bergamini, Cecilia Prata, Romana Fato, Riccardo Amorati, Zongxin Jin, Giovanna Farruggia, Diana Fiorentini*, Natalia Calonghi * and Chiara Zalambani.“Myrcene: A Natural Compound Showing Anticancer Activity in HeLa Cells” Molecules 2023, 28, 6728. https://doi.org/10.3390/molecules28186728
• Fiorentini D, Cappadone C, Farruggia G, Prata C. “Magnesium: Biochemistry, Nutrition, Detection, and Social Impact of Diseases Linked to Its Deficiency.” Nutrients. 2021 Mar 30;13(4):1136. doi: 10.3390/nu13041136. PMID: 33808247; PMCID: PMC8065437.