The globalization of medical research and care is advancing at a rapid pace, and we are already reaching the point at which both advanced medical development and everyday medical treatment (production of standard treatments and clinical practice guidelines) will be impossible in the absence of international cooperation. Based on the Agreement for Academic Exchanges and Cooperation and Memorandum on Student Exchange between University of Liege and Gunma University Graduate School of Medicine concluded on Oct. 2/2014, our laboratory (University of Liege) was opened in 2014 at the start. The laboratory has expanded into a mixing unit of UL and University of Montpellier oncology research group (Institute of Cancer Research of Montpellier/University of Montpellier) since Apr. 2017 (the Agreement and memorandum was concluded on Apr. 10/2017) to conduct world leading research. Our attention has been mainly focused on molecular cancer biology which can lead to discovery of drug targets and biomarkers for intractable malignant diseases.
* Cancer cell-mediated programing of fibroblasts from defensive to collaborative phenotype in clonal selection
* Cancer and Metabolism
* Development of patient-derived xenograft (PDTX) model that can maintain the functional stability of human metabolic phenotype
* Heterogeneity of intra-tumor and metastatic malignancies
* A novel non-destructive methodology for mining soluble biomarkers in clinically precious fresh human tissues
* Crosstalk of KRAS Mutated Cancer Cells with their Microenvironment in Colorectal Cancer
1. Chiavarina B, Turtoi A, Castronovo V,et al. Methylglyoxal-Mediated Stress Correlates with High Metabolic Activity and Promotes Tumor Growth in Colorectal Cancer. Int J Mol Sci. 2017 Jan 21;18(1). pii: E213. doi: 10.3390/ijms18010213.
2. Blomme A, Costanza B, Castronovo V, Turtoi A. Myoferlin is a novel exosomal protein and functional regulator of cancer-derived exosomes. Oncotarget. 36(15):2116-2130, 2017.
3. Nokin MJ, Chiavarina B, Turtoi A, Costanza B, Castronovo V, et al. Methylglyoxal, a glycolysis side-product, induces Hsp90 glycation and YAP-mediated tumor growth and metastasis. Elife. 2016 Oct 19;5. pii: e19375. doi: 10.7554/eLife.19375.
4. Blomme A, Costanza B, Yokobori T, Nishiyama M, Castronovo V, Turtoi A, et al. Myoferlin regulates cellular lipid metabolism and promotes metastases in triple-negative breast cancer. Oncogene. 2017;36(15):2116.
5. Henry A, Turtoi A, Castronovo V, et al. HDAC7 inhibition resets STAT3 tumorigenic activity in human glioblastoma independently of EGFR and PTEN: new opportunities for selected targeted therapies. Oncogene. 2016;35(34):4481.
6. Fahmy K, Turtoi A, Castronovo V, et al. Myoferlin plays a key role in VEGFA secretion and impacts tumor-associated angiogenesis in human pancreas cancer. Int J Cancer. 2016;138(3):652.
7. Peixoto P, Blomme A, Costanza B, Ronca R, Rezzola S, Palacios AP, Schoysman L, Boutry S, Goffart N, Peulen O, Maris P, Di Valentin E, Hennequière V, Bianchi E, Henry A, Rogister B, Muller R, Delvenne P, Bellahcene A, Castronovo V, Turtoi A. HDAC7 resets STAT3 tumorigenic activity in human glioblastoma independently of EGFR and PTEN status: new opportunities for selected targeted therapies. Oncogene. 35(34):4481-94. 2016.
8.Blomme A, Cusumano P, Peulen O, Bellahcène A, Castronovo V, Turtoi A. Asporin – The Protective Wall Against Triple Negative Breast Cancer. Med Sci (Paris), 32(11):1019-1022, 2016.
9. Turtoi A, Blomme A, Castronovo V. Intratumoral heterogeneity and consequences for targeted therapies. Bull Cancer, 102(1):17-23, 2015.
10. Lamour V, Turtoi A, Castronovo V, et al. Targeting osteopontin suppresses glioblastoma stem-like cell character and tumorigenicity in vivo. Int J Cancer. 2015;137(5):1047.
11. Maris P, Costanza B, Castronovo V, Turtoi A. Asporin Is a Fibroblast-Derived TGF-β1 Inhibitor and a Tumor Suppressor Associated with Good Prognosis in Breast Cancer. PLoS Med. 2015 Sep 1;12(9):e1001871. doi: 10.1371/journal.pmed.1001871. eCollection 2015 Sep.
12. Turtoi A, Blomme A, Bianchi E, Maris P, Vannozzi R, Naccarato AG, Delvenne P, De Pauw E, Bevilacqua G, Castronovo V. Accessibilome of Human Glioblastoma: Collagen-VI-alpha-1 Is a New Target and a Marker of Poor Outcome. J Proteome Res, 13(12):5660-9, 2014.
13. Chiavarina B, Nokin MJ, Durieux F, Bianchi E, Turtoi A, Peulen O, Peixoto P, Irigaray P, Uchida K, Belpomme D, Delvenne P, Castronovo V, Bellahcène A. Triple negative tumors accumulate significantly less methylglyoxal specific adducts than other human breast cancer subtypes. Oncotarget, 5(14):5472-82, 2014.
1. Costanza B, Umelo IA, Bellier J, Castronovo V, Turtoi A. Stromal Modulators of TGF-β in Cancer. J Clin Med. 2017 Jan 6;6(1). pii: E7. doi: 10.3390/jcm6010007. Review.
2. Turtoi A, Peixoto P, Castronovo V, Bellahcène A. Histone deacetylases and cancer-associated angiogenesis: current understanding of the biology and clinical perspectives. Crit Rev Oncog. 2015;20(1-2):119-37. Review.
The body of research concerning metastasis continues to grow at a rapid rate, but the biological programs are beginning to come into view. Tumors are complex tissues composed of multiple distinct cell types that participate in heterotypic interactions with one another, and the normal cells, which form tumor-associated stroma, are active participants in biological process. We continue the attempt to elucidate the crosstalk mechanisms and the critical determinants as a possible novel therapeutic target, especially focusing on exosomal proteins which regulate cancer-derived exosomes. Much efforts have focused on targeting oncogenic drivers located on signal transduction, while oncogenic events can also be located in other systems of the cancer biology. Targeted therapies can be effective in treating cancer, but drug resistance is inevitable. Secondary genomic events: how and when to track them? How to target other systems of cancer biology beyond oncogene de-addiction. This will be our next project. These studies will not be completed without multi-omics analyses. Working together with the whole GIAR programs, especially with the Research Program for Omics-based Medical Science, and Gunma University Graduate School of Medicine, we should expand our research filed and enhance our efforts in addressing important challenges. Actually our short-time interval exchange program of researchers such as PI, post-doctoral fellows, and post graduate students, between Gunma University and Montpellier/Liege research groups are greatly effective to promote our research projects with sharing advanced research fields where each institution has already great strengths.