Chaperone proteins in cancer growth and progression
Prof.ssa Mara Brancaccio (Principal Investigator)
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Activities(https://brancacciolab.com/) Cancer cells survive in a challenging environment, adapting to hypoxia, starvation and hostile physico-chemical conditions and experiencing proteotoxic stress due to the expression of mutant proteins and to the hyperactivation of signal transduction pathways. Indeed, cancer cells overexpress and are addicted to chaperone proteins. We are interested in studying the role of chaperone proteins in cancer growth and progression and in deciphering the molecular mechanisms by which their activity impacts on tumor biology.In the last years, we focused our studies on Morgana, a ubiquitously-expressed HSP90 co-chaperone protein, essential for mouse and Drosophila development. Morgana is a peculiar chaperone, since it behaves both as an oncosuppressor and as a proto-oncogene depending on the specific cellular context. Low Morgana expression levels, by inducing ROCK hyperactivation, promote centrosome overduplication and genomic instability in myeloid cells, causing the onset of atypical chronic myeloid leukemia. On the other hand, Morgana overexpression in solid tumors induces tumor cell survival, chemoresistance and cancer progression through the ROCK I-PTEN-AKT axis and the activation of the NF-kB pathway. (https://brancacciolab.com/cancer/) |
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Fusella F, Seclì L, Cannata C, Brancaccio M. The one thousand and one chaperones of the NF-κB pathway. Cell Mol Life Sci. 2019 Dec 6. doi: 10.1007/s00018-019-03402-z. [Epub ahead of print] Review. Fusella F, Seclì L, Brancaccio M. Escaping NK cells and recruiting neutrophils: How Morgana/NF-κB signaling promotes metastasis. Mol Cell Oncol. 2018 Jan 30;5(3):e1432258. doi: 10.1080/23723556.2018.1432258. eCollection 2018. PubMed PMID: 30250889. Rocca S, Carrà G, Poggio P, Morotti A, Brancaccio M. Targeting few to help hundreds: JAK, MAPK and ROCK pathways as druggable targets in atypical chronic myeloid leukemia. Mol Cancer. 2018 Feb 19;17(1):40. doi:10.1186/s12943-018-0774-4. Review. PubMed PMID: 29455651. Fusella F, Seclì L, Busso E, Krepelova A, Moiso E, Rocca S, Conti L, Annaratone L, Rubinetto C, Mello-Grand M, Singh V, Chiorino G, Silengo L, Altruda F, Turco E, Morotti A, Oliviero S, Castellano I, Cavallo F, Provero P, Tarone G, Brancaccio M. The IKK/NF-κB signaling pathway requires Morgana to drive breast cancer metastasis. Nat Commun. 2017 Nov 21;8(1):1636. doi:10.1038/s41467-017-01829-1. PubMed PMID: 29158506. Morotti A, Rocca S, Carrà G, Saglio G, Brancaccio M. Modeling myeloproliferative neoplasms: From mutations to mouse models and back again. Blood Rev. 2016 Nov 24. pii: S0268-960X(16)30034-0. doi: 10.1016/j.blre.2016.11.004 Brancaccio, M., Rocca, S., Secli, L., Busso, E. and Fusella, F. The double face of Morgana in tumorigenesis. Oncotarget. 2015 Dec 15;6(40):42603-12. doi: 10.18632/oncotarget.6058. Di Savino A, Panuzzo C, Rocca S, Familiari U, Piazza R, Crivellaro S, Carrà G, Ferretti R, Fusella F, Giugliano E, Camporeale A, Franco I, Miniscalco B, Cutrin JC, Turco E, Silengo L, Hirsch E, Rege-Cambrin G, Gambacorti-Passerini C, Pandolfi PP, Papotti M, Saglio G, Tarone G, Morotti A, Brancaccio M. Morgana acts as an oncosuppressor in chronic myeloid leukemia. Blood. 2015 Feb 12. pii: blood-2014-05-575001. Epub 2015 Feb 12. Fusella F, Ferretti R, Recupero D, Rocca S, Di Savino A, Tornillo G, Silengo L, Turco E, Cabodi S, Provero P, Pandolfi PP, Sapino A, Tarone G, Brancaccio M. Morgana acts as a proto-oncogene through inhibition of a ROCK-PTEN pathway. J Pathol. 2014 Oct;234(2):152-63. doi: 10.1002/path.4341. Epub 2014 Aug 6. Ferretti R, Palumbo V, Di Savino A, Velasco S, Sbroggiò M, Sportoletti P, Micale L, Turco E, Silengo L, Palumbo G, Hirsch E, Teruya-Feldstein J, Bonaccorsi S, Pandolfi PP, Gatti M, Tarone G, Brancaccio M. Morgana/chp-1, a ROCK Inhibitor Involved in Centrosome Duplication and Tumorigenesis. (2010) Dev Cell 18: 486–495.
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We are deeply interested in two different lines of research. On the one hand, we are investigating the role of morgana in tumor onset and progression, by dissecting the molecular mechanisms involved in morgana action. On the other hand, we are involved in understanding the molecular basis of maladaptive versus compensatory remodeling in the heart subjected to stress, where melusin may represent an important protective agent.
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