024 | In vitro analysis of molecular chaperone involvement in the radiological response of triple-negative breast cancer models

Giusi Alberti¹, Giuseppe Vergilio¹, Domiziana Picone¹, Denise Amico¹, Rosario Barone¹, Francesca Rappa¹, Marco Calvaruso³, Gaia Pucci³, Luigi Minafra³, Antonella Marino Gammazza² | ¹Department of Biomedicine, Neuroscience and Advanced Diagnostic BIND, University of Palermo, Italy; ²Department of Biological, Chemical and Pharmaceutical Sciences and Technologies STEBICEF, University of Palermo, Italy; ³Institute of Bioimaging and Complex Biological Systems-National Reasearch Council IBSBC-CNR, Cefalù-Palermo, Italy.

Triple-negative breast cancer (TNBC) is an aggressive subtype characterized by high recurrence rates and resistance to conventional therapies, including radiation therapy (RT). Despite RT being a standard of care, acquired radioresistance remains a significant clinical obstacle [1]. Molecular chaperones are play pivotal roles in protein folding, anti-apoptotic signaling, and therapy resistance. Specifically, Hsp27, Hsp60, and Hsp90 have been implicated in promoting pro-survival pathways and modulating the cellular response to stress [2]. In this study, we evaluated the response of three established TNBC cell lines—MDA-MB-231, SUM-159, and BT-549—to a single dose of 5 Gy irradiation. We analyzed the expression levels and subcellular distribution of Hsp27, Hsp60, and Hsp90 using morphological and molecular biology techniques to determine their involvement in the acute radiological response. Preliminary data indicate that ionizing radiation triggers distinct chaperone dynamics across the tested cell lines. The study highlights how the dysregulation of these molecular chaperones correlates with the activation of complex signaling networks that drive tumor survival and adaptation under therapeutic pressure. Our findings suggest that Hsp27, Hsp60, and Hsp90 are key players in the TNBC radiation response. Identifying specific expression patterns of these proteins may provide a panel of predictive radiosensitivity biomarkers, offering a valuable tool for clinicians to optimize and personalize treatment plans for TNBC patients.
This study was funded by Unione europea—Next Generation EU, Missione 4 Componente 1, CUP B53D23020620006—CUP B53D23020630006 - Ministero Italiano dell’Università e della Ricerca, PRIN 2022, Grant no. 2022PW8R47 to Luigi Minafra and Antonella Marino Gammazza.