Brönnimann Daniel, Annese Tiziana, Gorr Thomas A., Djonov Valentin (2018), Splitting of circulating red blood cells as in vivo -mechanism of erythrocyte maturation in developing zebrafish, chick and mouse embryos, in The Journal of Experimental Biology
Breasson Ludovic, Sardi Claudia, Becattini Barbara, Zani Fabio, Solinas Giovanni (2018), PI3Kγ ablation does not promote diabetes in db/db mice, but improves insulin sensitivity and reduces pancreatic β-cell apoptosis, in The FASEB Journal
, 32(1), 319-329.
Solinas Giovanni, Becattini Barbara (2017), The role of PI3Kgamma in metabolism and macrophage activation, in Oncotarget
, 8(63), 106145-106146.
Hlushchuk Ruslan, Styp-Rekowska Beata, Dzambazi Jehona, Wnuk Monika, Huynh-Do Uyen, Makanya Andrew, Djonov Valentin (2017), Endoglin inhibition leads to intussusceptive angiogenesis via activation of factors related to COUP-TFII signaling pathway, in PLOS ONE
, 12(8), e0182813-e0182813.
Solinas Giovanni (2017), JNK at the crossroad of obesity, insulin resistance, and cell stress response., in Mol Metab
, 6(2), 174-184.
Breasson Ludovic, BecattiniBarbara, SardiClaudia, MolinaroAngela, ZaniFabio, MaroneRomina, BotindariFabrizio, BousquenaudMélanie, RueggCurzio, WymannMatthias, SolinasGiovanni (2017), PI3Kγ activity in leukocytes promotes adipose tissue inflammation and early-onset insulin resistance during obesity., in Science signaling
Hlushchuk Ruslan, Barré Sébastien, Djonov Valentin (2016), Tumor Angiogenesis Assays
Djukic Tijana R., Karthik Swapna, Saveljic Igor, Djonov Valentin, Filipovic Nenad (2016), Modeling the Behavior of Red Blood Cells within the Caudal Vein Plexus of Zebrafish, in Frontiers in Physiology
, 7, 1-12.
Becattini Barbara, ZaniFabio, SardiClaudia, D'AgostinoVito Giuseppe, ChooMin-Kyung, ProvenzaniAlessandro, ParkJin Mo, SolinasGiovanni (2016), JNK1 ablation in mice confers long-term metabolic protection from diet-induced obesity at the cost of moderate skin oxidative damage., in FASEB J.
, ((9)), 3124-3132.
Obesity is a major risk factor for several cancers including of the colon, endometrium, pancreas, prostate, liver and post-menopausal breast cancer. The impact of obesity on cancer is a major public health concern because of the large and growing pandemic proportion of obesity. In addition obesity is a negative prognostic factor with impact on cancer treatments and outcome. For the future it will be of the utmost importance to identify cancer treatments specifically tailored for overweight and obese patients. In spite of the clinical relevance, the mechanism by which obesity promotes cancer initiation and progression remains largely elusive. Although cancer initiation and progression requires the activation of tumor promoting genes (oncogenes) and the inactivation of tumor suppressor genes through genetic and epigenetic events, additional factors within the host provide an important and some times essential contribution to tumorigenesis. Bone marrow-derived inflammatory cells newly recruited at the tumor site and resident leukocytes are instrumental to inflammatory events contributing to tumor initiation and progression. The formation of a tumor-associated vasculature, a process also know as tumor angiogenesis, facilitates primary tumor growth and metastasis formation. In this project three established investigators, Pr C. Rüegg, Dr. G. Solinas and Pr V. Djonov with related but complementary research interests and expertise are joining forces to investigate host-dependent mechanisms of obesity-mediated tumor initiation and promotion. PI3K-Akt is a critical signaling node in mechanisms modulating metabolism, obesity, inflammation, angiogenesis and cancer relevant to obesity-mediated tumor promotion. In this project we will generate and use mice lacking three different isozymes of PI3K (beta, gamma, delta) in hematopoietic/inflammatory and endothelial cells, to test the role of these PI3K isozymes in obesity mediated promotion of hepatocellular carcinoma, breast cancer progression and metastasis, and intussusceptive angiogenesis. The specific subprojects are:1) Investigating the role of PI3K signaling in obesity-mediated promotion of hepatocellular carcinoma (Solinas)2) Role of class-1 PI3K signaling within hematopoietic and endothelial cells in obesity-mediated breast cancer progression (Rüegg)2) Intussusceptive angiogenesis - an alternative way of blood vessel formation in obesity driven tumor initiation and progression (Djonov)We envisage that results obtained in this project will have important implications toward a better understanding of the mechanisms of cancer initiation and progression, which may be fundamental to better tumor prevention or cancer treatment for overweight and obese individuals.