Gene expression control in tumor biology
Valeria Poli (Pricipal Investigator)
Controlled production of cytokines and growth factors, leading to the activation of specific signalling pathways and to the modulation of gene expression, is essential for life. However, aberrant cytokines/growth factors production or altered regulation of their signalling and/or of the activity of the downstream transcription factors are at the basis of many pathological conditions including chronic inflammation, auto-immunity and oncogenesis. The laboratory has long focused on the axis between the pro-inflammatory cytokine IL-6 and the oncogenic transcription factor STAT3 at the crossroads between inflammation, auto-immunity and cancer, aiming at characterizing STAT3 involvement in both physiological and pathological conditions and making use of both in vitro approaches and in vivo genetically modified mouse model (GEMMs). In recent years we have demonstrated that constitutively active STAT3 can cooperate with oncogenes such as the HER2/Neu to confer aggressive features to breast tumors and support metastasis formation (Barbieri et al., 2010open_in_new, Barbieri et al., 2010open_in_new). Moreover, we have shown that aberrantly active STAT3 can regulate energy metabolism and mitochondrial activity and can act as a first hit in tumor transformation, shedding light on its well-known central role in inflammation-induced tumorigenesis (Demaria et al., 2010open_in_new, Demaria et al, 2012open_in_new).
Main ongoing research projects focus on different aspects of cancer biology, and in particular:
- STAT3-dependent and independent mechanisms of cross-talk between tumor cells and Cancer Associated Fibroblasts (CAFs) in breast cancer. In a project supported by AIRC, we have identified several STAT3-dependent genes encoding for secreted proteins responsible of CAFs pro-oncogenic functions and we are assessing the feasibility of targeting them for therapeutic purposes (Avalle et al., submitted).
- Identification of regulatory networks and novel therapeutic targets in breast cancer. Supported by a donation from TRUUS AND GERRIT VAN RIEMSDIJK FOUNDATION, VADUZ, LIECHTENSTEIN, and by AIRC 2020. We have generated co-expression networks based on large breast cancer gene expression databases, and identified several hubs of these network as crucial regulators of breast cancer aggressiveness features. Functional validation and assessment of inhibitory strategies as therapeutic approach is in progress.
- Disentangling the relationships with tumor microenvironment in prostate cancer to better model and target tumor progression. This is a collaborative effort with the Universities of Varese, Trento, Trieste, Catanzaro, and with the CNR of Lecce supported by a MIUR/PRIN 2017 grant, based on the analysis of CAFs and tumor cells/organoids derived from high risk patient samples.
- Validation and improvement of cancer neoantigen vaccines. This is a collaboration with Nouscomopen_in_new, based on assessing and improving the immunogenicity and effectiveness of personalized neoantigen vaccines in a mouse model (D'Alise et al., 2019).open_in_new
- Novel intergenic long non coding (linc) RNAs involved in maintaining ES cells stemness. We have identified two uncharacterized STAT3-dependent lincRNAs as fundamental players in maintaining ES cells in an undifferentiated state, and are trying to understand their correlations with tumorigenesis (Monterelone et al, MS in preparation).
- Prof.ssa Valeria Poli (PI)
- Dr. Lidia Avalle (post-doctoral fellow)
- Dr. Aurora Savino (Ph.D. student)
- Miss Simona Averasano Stabile (graduate student)
- Miss Giulia Accetta (graduate student)
- Mr Daniele Viavattene (graduate student)
- Mr Alberto Griffa (undergraduate student)
- Mr Niccolò De Marzo (undergraduate student)