Slug/β-catenin-dependent proinflammatory phenotype in hypoxic breast cancer stem cells

Gianluca Storci; Sara Bertoni; Sabrina De Carolis; Alessio Papi; Marina Nati; Claudio Ceccarelli; Chiara Pirazzini; Paolo Garagnani; Alberto Ferrarini; Genny Buson; Massimo Delledonne; Michelangelo Fiorentino; Elisa Capizzi; Elisa Gruppioni; Mario Taffurelli; Donatella Santini; Claudio Franceschi; Giuseppe Bandini; Francesca Bonifazi; Massimiliano Bonafé

doi:10.1016/j.ajpath.2013.07.020

Slug/β-catenin-dependent proinflammatory phenotype in hypoxic breast cancer stem cells

Gianluca Storci, Sara Bertoni, Sabrina De Carolis, Alessio Papi, Marina Nati, Claudio Ceccarelli, Chiara Pirazzini, Paolo Garagnani, Alberto Ferrarini, Genny Buson, Massimo Delledonne, Michelangelo Fiorentino, Elisa Capizzi, Elisa Gruppioni, Mario Taffurelli, Donatella Santini, Claudio Franceschi, Giuseppe Bandini, Francesca Bonifazi, Massimiliano Bonafé

Istituto Scienze Neurologiche

Research output: Contribution to journal › Article

Abstract

Cancer stem cell survival relies on the activation of inflammatory pathways, which is speculatively triggered by cell autonomous mechanisms or by microenvironmental stimuli. Here, we observed that hypoxic bone marrow stroma-derived transforming growth factor-β 1 promotes the growth of human breast cancer stem cells as mammospheres. The ensuing Slug-dependent serine 139 phosphorylation of the DNA damage sensor H2AX in breast cancer stem cells induces tumor necrosis factor-α and IL-8 mRNAs, whose stability is enhanced by cytoplasmic β-catenin. β-Catenin also up-regulates and binds miR-221, reducing the stability of the miR-221 targets Rad51 and ERα mRNAs. Our data show that the Slug/β-catenin-dependent activation of DNA damage signaling triggered by the hypoxic microenvironment sustains the proinflammatory phenotype of breast cancer stem cells.

Original language	English
Pages (from-to)	1688-1697
Number of pages	10
Journal	American Journal of Pathology
Volume	183
Issue number	5
DOIs	https://doi.org/10.1016/j.ajpath.2013.07.020
Publication status	Published - Nov 2013

ASJC Scopus subject areas

Pathology and Forensic Medicine

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Storci, G., Bertoni, S., De Carolis, S., Papi, A., Nati, M., Ceccarelli, C., Pirazzini, C., Garagnani, P., Ferrarini, A., Buson, G., Delledonne, M., Fiorentino, M., Capizzi, E., Gruppioni, E., Taffurelli, M., Santini, D., Franceschi, C., Bandini, G., Bonifazi, F., & Bonafé, M. (2013). Slug/β-catenin-dependent proinflammatory phenotype in hypoxic breast cancer stem cells. American Journal of Pathology, 183(5), 1688-1697. https://doi.org/10.1016/j.ajpath.2013.07.020

Slug/β-catenin-dependent proinflammatory phenotype in hypoxic breast cancer stem cells. / Storci, Gianluca; Bertoni, Sara; De Carolis, Sabrina; Papi, Alessio; Nati, Marina; Ceccarelli, Claudio; Pirazzini, Chiara; Garagnani, Paolo; Ferrarini, Alberto; Buson, Genny; Delledonne, Massimo; Fiorentino, Michelangelo; Capizzi, Elisa; Gruppioni, Elisa; Taffurelli, Mario; Santini, Donatella; Franceschi, Claudio; Bandini, Giuseppe; Bonifazi, Francesca; Bonafé, Massimiliano.

In: American Journal of Pathology, Vol. 183, No. 5, 11.2013, p. 1688-1697.

Research output: Contribution to journal › Article

Storci, G, Bertoni, S, De Carolis, S, Papi, A, Nati, M, Ceccarelli, C, Pirazzini, C, Garagnani, P, Ferrarini, A, Buson, G, Delledonne, M, Fiorentino, M, Capizzi, E, Gruppioni, E, Taffurelli, M, Santini, D, Franceschi, C, Bandini, G, Bonifazi, F & Bonafé, M 2013, 'Slug/β-catenin-dependent proinflammatory phenotype in hypoxic breast cancer stem cells', American Journal of Pathology, vol. 183, no. 5, pp. 1688-1697. https://doi.org/10.1016/j.ajpath.2013.07.020

Storci, Gianluca ; Bertoni, Sara ; De Carolis, Sabrina ; Papi, Alessio ; Nati, Marina ; Ceccarelli, Claudio ; Pirazzini, Chiara ; Garagnani, Paolo ; Ferrarini, Alberto ; Buson, Genny ; Delledonne, Massimo ; Fiorentino, Michelangelo ; Capizzi, Elisa ; Gruppioni, Elisa ; Taffurelli, Mario ; Santini, Donatella ; Franceschi, Claudio ; Bandini, Giuseppe ; Bonifazi, Francesca ; Bonafé, Massimiliano. / Slug/β-catenin-dependent proinflammatory phenotype in hypoxic breast cancer stem cells. In: American Journal of Pathology. 2013 ; Vol. 183, No. 5. pp. 1688-1697.

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abstract = "Cancer stem cell survival relies on the activation of inflammatory pathways, which is speculatively triggered by cell autonomous mechanisms or by microenvironmental stimuli. Here, we observed that hypoxic bone marrow stroma-derived transforming growth factor-β 1 promotes the growth of human breast cancer stem cells as mammospheres. The ensuing Slug-dependent serine 139 phosphorylation of the DNA damage sensor H2AX in breast cancer stem cells induces tumor necrosis factor-α and IL-8 mRNAs, whose stability is enhanced by cytoplasmic β-catenin. β-Catenin also up-regulates and binds miR-221, reducing the stability of the miR-221 targets Rad51 and ERα mRNAs. Our data show that the Slug/β-catenin-dependent activation of DNA damage signaling triggered by the hypoxic microenvironment sustains the proinflammatory phenotype of breast cancer stem cells.",

author = "Gianluca Storci and Sara Bertoni and {De Carolis}, Sabrina and Alessio Papi and Marina Nati and Claudio Ceccarelli and Chiara Pirazzini and Paolo Garagnani and Alberto Ferrarini and Genny Buson and Massimo Delledonne and Michelangelo Fiorentino and Elisa Capizzi and Elisa Gruppioni and Mario Taffurelli and Donatella Santini and Claudio Franceschi and Giuseppe Bandini and Francesca Bonifazi and Massimiliano Bonaf{\'e}",

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AU - Ceccarelli, Claudio

AU - Pirazzini, Chiara

AU - Garagnani, Paolo

AU - Ferrarini, Alberto

AU - Buson, Genny

AU - Delledonne, Massimo

AU - Fiorentino, Michelangelo

AU - Capizzi, Elisa

AU - Gruppioni, Elisa

AU - Taffurelli, Mario

AU - Santini, Donatella

AU - Franceschi, Claudio

AU - Bandini, Giuseppe

AU - Bonifazi, Francesca

AU - Bonafé, Massimiliano

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