Research

Metabolic profile and redox homeostasis of tumor cells

One of the key hallmarks of cancer cells is sustained growth and proliferation, which require a complex metabolic rewiring with an enhancement of anabolic pathways and a profound alteration of redox homeostasis. Our previous studies reinforced and expanded these concepts in the context of T-cell neoplasms.

Current studies:
By using a combination of biochemistry, molecular and cellular biology as well as preclinical in vivo models, the current experimental projects are aimed at gaining insight into the general mechanisms of T-cell transformation and to develop tumor-specific therapies that exploit the higher ROS (reactive oxygen species) set-point of tumor cells to target pediatric T-ALL (T-acute lymphoblastic leukemia). As 25% of T-ALL patients respond poorly to current therapies and have a dismal prognosis, new effective therapies against these neoplasms are in high demand.

5 selected publications
Silic-Benussi M, Scattolin G, Cavallari I, Minuzzo S, del Bianco P, Francescato S, Basso G, Indraccolo S, D’Agostino DM and Ciminale V. Selective killing of human T-ALL cells: an integrated approach targeting redox homeostasis and the OMA1/OPA1 axis. Cell Death and Disease, 2018, in press.

Ciccarese F, Ciminale V. Escaping Death: Mitochondrial Redox Homeostasis in Cancer Cells. Front Oncol. 2017 Jun 9; 7:117.

D'Agostino DM, Zanovello P, Watanabe T, and Ciminale V. (2012) The microRNA regulatory network in normal- and HTLV-1-transformed T cells. Adv Cancer Res.; 113:45-83.

Rende F, Cavallari I, Corradin A, Silic-Benussi M, Toulza F, Toffolo GM, Tanaka Y, Jacobson S, Taylor GP, D'Agostino DM, Bangham CR, and Ciminale V. (2011) Kinetics and intracellular compartmentalization of HTLV-1 gene expression: nuclear retention of HBZ mRNA. Blood. 117:4855-9. 

Silic-Benussi M, Cavallari I, Vajente N, Vidali S, Chieco-Bianchi L, Di Lisa F, Saggioro D, D’Agostino DM and Ciminale V. (2010) Redox regulation of T-cell turnover by the p13 protein of human T-cell leukemia virus type 1: distinct effects in primary vs. transformed cells. Blood, 116:54-62.

Funding
AIRC
Istituto Oncologico Veneto 5 x 1000

Personnel involved
Vincenzo Ciminale, Associate Professor

Group members
Ilaria Cavallari, IOV Fellow
Micol Silic-Benussi, IOV Fellow
Francesco Ciccarese, Assegnista
Gloria Scattolin, PhD student