Salta al contenuto principale

Cancer Metabolism and Cachexia (CaMeCa)

Paolo E. Porporato
Paolo E. Porporato PI

Biographical sketch 

Associate Professor in Experimental Biology at the University of Turin, Torino, Italy 

Main group members
Main group members

  • Elisabeth Wyart Post-Doc

  • Erica Mina PhD Student

  • Rita Vacca Research Fellow

  • Ivan Zaggia Research Fellow

  • Roberta Basile Research Fellow

Research activity

Our research focuses on the role of metabolism in shaping biological function, with a particular focus on muscle biology. At the Cancer Metabolism and Cachexia (CaMeCa) Lab, we investigate the metabolic interactions that connect muscle physiology, cancer cells, immune landscapes, and the host. 

We pursue this goal through three complementary research lines (Figure 1):

  • Cachexia and Muscle–Tumor Crosstalk – We study how skeletal muscle, far from being a passive victim of cancer, acts as an active metabolic organ that shapes systemic disease progression. We have identified profound alterations in muscle iron metabolism during tumor growth, characterized by mitochondrial iron deficiency and atrophy. Modulation of iron levels directly influences myotube size, muscle mass, and overall survival in tumor-bearing mice. In addition, we are dissecting how the muscle secretome mediates communication between muscle and tumors, driving metastasis, inflammation, and systemic wasting.
  • Cancer Metabolism – We investigate iron metabolism as a central vulnerability in cancer. Our recent data demonstrate that iron supplementation can remodel tumor metabolism, induce oxidative stress in cancer cells, and restore iron availability in immune and skeletal muscle compartments. This dual effect reduces tumor growth, potentiates anti-tumor immunity, and counteracts cancer-induced cachexia. We are expanding this work through CRISPR-based functional genomics to uncover synthetic lethal interactions in lung cancer, paving the way for novel therapeutic strategies targeting metabolic iron homeostasis.
  • Space Medicine – Leveraging our expertise in muscle metabolism, we investigate the mechanisms of microgravity-induced muscle atrophy as a model of extreme physiological stress. Using advanced in vitro models, we study how the TGFβ/BMP–Smad signaling axis and mitochondrial pathways regulate muscle mass under disuse and develop pharmacological countermeasures such as low-dose FK506 to preserve muscle function and neuromuscular junction integrity during spaceflight.

Through these integrated projects, we strive to understand how metabolism governs the dialogue between tumors, muscle, and the immune system, and how these mechanisms are challenged under extreme conditions such as microgravity. By linking cancer biology, cachexia research, and space medicine, our goal is to translate fundamental metabolic discoveries into strategies that improve human health and performance across various pathological and environmental conditions.

To this aim, we are working on multiple fronts to address various aspect of this metabolic interactions: i) to study the mitochondrial metabolism of alternative amino acids as central player in the complex web of cancer aggressiveness and immune escape. Expanding our knowledge of these processes will provide opportunities for innovative cancer treatments that will disrupt cancer cell energetics and restore the immune system’s ability to recognize and eliminate malignant cells. This intersection of metabolism and immunology holds great promise in the ongoing battle against cancer; ii) to understand the impact of altered metabolic activities in skeletal muscle on the development of tumor and its aggressiveness.

  • Bando POC-TOINPROVE 
  • Bando POC-LIFFT on the development of proprietary patent Novel BMP modulators and use thereof. 
  • Bando MFAG-AIRC My First AIRC Grant. “Targeting crosstalk between muscle and cancer” (2019-2024), 
  • Fondo Rita Levi-Montalcini 2014 “Understanding and targeting cancer-related muscle atrophy” (2016-2019) 
  • Bando Finalizzata Giovani Ricercatori (2023-26): “NF-Kb positively regulates Fatty Acid Oxidation in cancer cells, which hinders CD8+ T lymphocytes and promotes tumor progression”. PI: Alessio Menga. GR2021-12374957
  • Bando MFAG-AIRC My First AIRC Grant (2021-26): “Dissecting mitochondrial lysine and tryptophan metabolism to target metabolic symbiosis in lung adenocarcinoma”. PI: Alessio Menga MFAG, Rif. 25908
  • Wyart E, Hsu M, Sartori R, Mina E, Rausch V, Pierobon ES, Mezzanotte M, Pezzini C, Bindels LB, Penna F, Lauria A, Filigheddu N, Hirsch E, Martini M, Roetto A, Geninatti-Crich S, Prenen H, Mazzone M, Sandri M, Menga A, and Porporato PE. Iron supplementation is sufficient to rescue cancer-induced muscle wasting and function. EMBO Reports, e53746 (2022) 
  • Wyart E, Reano S, Longo D, Ghigo A, Riganti C, Porporato PE. Metabolic characterization of a new model of PDAC-induced cancer cachexia, Oxid Med Cell Longev. 2018 Feb 26; 
  • Payen VL, Hsu MY, Rädecke KS, Wyart E, Vazeille T, Bouzin C, Porporato PE* Sonveaux P. Monocarboxylate Transporter MCT1 Promotes Tumor Metastasis Independently of Its Activity as a Lactate Transporter. Cancer Res 2017;77(20):5591-5601. doi: 10.1158/0008- 5472.CAN-17-0764. *co-last 
  • Porporato PE, Filigheddu N, Pedro JMB, Kroemer G, Galluzzi L. Mitochondrial metabolism and cancer. Cell Res. 2018 Mar;28(3):265-280. 
  • Brisson L, Bański P, Sboarina M, Dethier C, Danhier P, Fontenille MJ, Van Hée VF, Vazeille T, Tardy M, Falces J, Bouzin C, Porporato PE, Frédérick R, Michiels C, Copetti T, Sonveaux P. Lactate Dehydrogenase B Controls Lysosome Activity and Autophagy in Cancer. Cancer Cell 2016 
  • Porporato PE, Filigheddu N, Reano S, Ferrara M, Angelino E, Gnocchi V, Prodam F, Ronchi G, Fagoone S, Chianale F, Chianale F, Baldanzi G, Sinigaglia F, Surico N, Perroteau I, Smith R, Sun Y, Geuna S, Graziani A. Acylated and unacylated ghrelin impair skeletal muscle atrophy in mice. J Clin Invest. 2013 Jan 2;123(2):611- 22. 
  • Porporato PE, Payen VL, De Saedeleer CJ, Préat V, Thissen JP, Feron O, Sonveaux P. Lactate stimulates angiogenesis and accelerates the healing of superficial and ischemic wounds in mice. Angiogenesis. 2012 Jun 3;15(4):581-92. 
  • Menga A, Favia M, Spera I, Vegliante MC, Gissi R, De Grassi A, Laera L, Campanella A, Gerbino A, Carrà G, Canton M, Loizzi V, Pierri CL, Cormio G, Mazzone M, Castegna A. N-acetylaspartate release by glutaminolysis ovarian cancer cells sustains protumoral macrophages. EMBO Rep. 2021 Jul 14:e51981. doi: 10.15252/embr.202051981. Epub ahead of print. PMID:34260142. 2-s2.0-85109871059 
  • Menga A, Serra M, Todisco S, et al. Glufosinate constrains synchronous and metachronous metastasis by promoting anti-tumor macrophages [published online ahead of print, 2020 Sep 4]. EMBO Mol Med. 2020; e 11210. doi:10.15252/emmm.201911210. 2-s2.0- 85090134974 
  • Palmieri EM, Menga A, Martín-Pérez R, Quinto A, Riera-Domingo C, De Tullio G, Hooper DC, Lamers WH, Ghesquière B, McVicar DW, Guarini A, Mazzone M & Castegna A (2017) Pharmacologic or Genetic Targeting of Glutamine Synthetase Skews Macrophages toward an M1-like Phenotype and Inhibits Tumor Metastasis. Cell Rep. 20, 1654–1666. 2-s2.0-85027849350 
Ultimo aggiornamento:
Share: