Prostate Cancer Biology
Group Leader: Carbone Giuseppina, MD
Research in our group is focused on the study of the molecular mechanisms that control prostate cancer development and progression. Cancer of the prostate is the most common cancer and one of leading causes of cancer related death. At the present there is a need to understand the mechanisms involved in the pathogenesis of this disease and find the means to distinguish between cancers that may need different therapeutic strategies. One of our goals is to identify and characterize the transcription factor cascade that control prostate cancer development. Cell growth and differentiation processes are regulated at the level of gene transcription. Many transcription factors possess transforming potential when expressed in a deregulated fashion. ETS factors constitute a network of transcriptional regulators that activate or repress the expression of genes that are involved in various biological processes, including cellular proliferation, apoptosis, invasiveness and cancer progression. The laboratory has identified ETS genes potentially involved in prostate cancer, based upon their altered expression in prostate cancer clinical samples. Currently, the functional role of these genes is being investigated as well as their relevance for diagnosis, prognosis and therapy. We are also investigating novel therapeutic approaches to target oncogenic ETS factors.
- Zoma M, Curti L, Shinde D, Albino D, Mitra A, Sgrignani J, Mapelli SN, Sandrini G, Civenni G, Merulla J, Chiorino G, Kunderfranco P, Cacciatore A, Kokanovic A, Rinaldi A, Cavalli A, Catapano CV and Carbone GM. EZH2-induced lysine K362 methylation enhances TMPRSS2-ERG oncogenic activity in prostate cancer. Nat Commun (2021) 12, 4147. https://www.ncbi.nlm.nih.gov/pubmed/34230470.
- Albino D, Falcione M, Uboldi V, Temilola DO, Sandrini G, Merulla J, Civenni G, Kokanovic A, Sturchler A, Shinde D, Garofalo M, Mestre RP, Constancio V, Wium M, Burrello J, Baranzini N, Grimaldi A, Theurillat JP, Bossi D, Barile L, Henrique RM, Jeronimo C, Zerbini LF, Catapano CV and Carbone GM. Circulating extracellular vesicles release oncogenic miR-424 in experimental models and patients with aggressive prostate cancer. Commun Biol (2021) 4, 119. https://www.ncbi.nlm.nih.gov/pubmed/33500545.
- Mapelli SN, Albino D, Mello-Grand M, Shinde D, Scimeca M, Bonfiglio R, Bonanno E, Chiorino G, Garcia-Escudero R, Catapano CV and Carbone GM. A Novel Prostate Cell Type-Specific Gene Signature to Interrogate Prostate Tumor Differentiation Status and Monitor Therapeutic Response (Running Title: Phenotypic Classification of Prostate Tumors). Cancers (Basel) (2020) 12. https://www.ncbi.nlm.nih.gov/pubmed/31936761.
- Shinde D, Albino D, Zoma M, Mutti A, Mapelli SN, Civenni G, Kokanovic A, Merulla J, Perez-Escuredo J, Costales P, Moris F, Catapano CV and Carbone GM. Transcriptional Reprogramming and Inhibition of Tumor-propagating Stem-like Cells by EC-8042 in ERG-positive Prostate Cancer. Eur Urol Oncol (2019) 2, 415-424. https://www.ncbi.nlm.nih.gov/pubmed/31277777.
- Dallavalle C, Albino D, Civenni G, Merulla J, Ostano P, Mello-Grand M, Rossi S, Losa M, D'Ambrosio G, Sessa F, Thalmann GN, Garcia-Escudero R, Zitella A, Chiorino G, Catapano CV and Carbone GM. MicroRNA-424 impairs ubiquitination to activate STAT3 and promote prostate tumor progression. J Clin Invest (2016) 126, 4585-4602. https://pubmed.ncbi.nlm.nih.gov/27820701/.
- Albino D, Civenni G, Dallavalle C, Roos M, Jahns H, Curti L, Rossi S, Pinton S, D'Ambrosio G, Sessa F, Hall J, Catapano CV and Carbone GM. Activation of the Lin28/let-7 Axis by Loss of ESE3/EHF Promotes a Tumorigenic and Stem-like Phenotype in Prostate Cancer. Cancer Res (2016) 76, 3629-3643. https://www.ncbi.nlm.nih.gov/pubmed/27197175.
- Longoni N, Sarti M, Albino D, Civenni G, Malek A, Ortelli E, Pinton S, Mello-Grand M, Ostano P, D'Ambrosio G, Sessa F, Garcia-Escudero R, Thalmann GN, Chiorino G, Catapano CV and Carbone GM. ETS transcription factor ESE1/ELF3 orchestrates a positive feedback loop that constitutively activates NF-kappaB and drives prostate cancer progression. Cancer Res (2013) 73, 4533-4547. https://www.ncbi.nlm.nih.gov/pubmed/23687337.
- Albino D, Longoni N, Curti L, Mello-Grand M, Pinton S, Civenni G, Thalmann G, D'Ambrosio G, Sarti M, Sessa F, Chiorino G, Catapano CV and Carbone GM. ESE3/EHF controls epithelial cell differentiation and its loss leads to prostate tumors with mesenchymal and stem-like features. Cancer Res (2012) 72, 2889-2900. https://www.ncbi.nlm.nih.gov/pubmed/22505649.
- Kunderfranco P, Mello-Grand M, Cangemi R, Pellini S, Mensah A, Albertini V, Malek A, Chiorino G, Catapano CV and Carbone GM. ETS transcription factors control transcription of EZH2 and epigenetic silencing of the tumor suppressor gene Nkx3.1 in prostate cancer. PLoS One (2010) 5, e10547. https://www.ncbi.nlm.nih.gov/pubmed/20479932.
- Cangemi R, Mensah A, Albertini V, Jain A, Mello-Grand M, Chiorino G, Catapano CV and Carbone GM. Reduced expression and tumor suppressor function of the ETS transcription factor ESE-3 in prostate cancer. Oncogene (2008) 27, 2877-2885. https://www.ncbi.nlm.nih.gov/pubmed/18037958.