FSP1 is a predictive biomarker of osteosarcoma cells’ susceptibility to ferroptotic cell death and a potential therapeutic target
Аутори
Panczyszyn, ElzbietaSaverio, Valentina
Monzani, Romina
Gagliardi, Mara
Petrović, Jelena
Stojkovska, Jasmina
Collavin, Licio
Corazzari, Marco
Чланак у часопису (Објављена верзија)
Метаподаци
Приказ свих података о документуАпстракт
Human osteosarcoma (OS) is a relatively rare malignancy preferentially affecting long body bones which prognosis is often poor also due to the lack of effective therapies. Clinical management of this cancer basically relies on surgical removal of primary tumor coupled with radio/chemotherapy. Unfortunately, most osteosarcoma cells are resistant to conventional therapy, with the undergoing epithelial-mesenchymal transition (EMT) giving rise to gene expression reprogramming, thus increasing cancer cell invasiveness and metastatic potential. Alternative clinical approaches are thus urgently needed. In this context, the recently described ferroptotic cell death represents an attractive new strategy to efficiently kill cancer cells, since most chemoresistant and mesenchymal-shaped tumors display high susceptibility to pro-ferroptotic compounds. However, cancer cells have also evolved anti-ferroptotic strategies, which somehow sustain their survival upon ferroptosis induction. Indeed, here w...e show that osteosarcoma cell lines display heterogeneous sensitivity to ferroptosis execution, correlating with the mesenchymal phenotype, which is consistently affected by the expression of the well-known anti-ferroptotic factor ferroptosis suppressor protein 1 (FSP1). Interestingly, inhibiting the activity or expression of FSP1 restores cancer cell sensitivity to ferroptosis. Moreover, we also found that: i) AKRs might also contribute to resistance; ii) NRF2 enhances FSP1 expression upon ferroptosis induction; while iii) p53 contributes to the regulation of FSP1 basal expression in OS cells. In conclusion, FSP1 expression can potentially be used as a valuable predictive marker of OS sensitivity to ferroptosis and as a new potential therapeutic target.
Извор:
Cell Death Discovery, 12-2024, 10, 1, 87-Издавач:
- Springer Nature
Финансирање / пројекти:
- Italian Ministry of Education, University and Research (MUR) program “Departments of Excellence 2018–2022”
- FOHN Project—Department of Health Sciences, Università del Piemonte Orientale
- MUR Progetti di Ricerca di Rilevante Interesse Nazionale (PRIN) Bando 2022 – grant 202285XS52 (to LC&MC)
- FAR 2019 (Progetti di Ateneo)
- EU grant “PREMUROSA” (ID #860462)
- “ExcellMater” (ID #952033) H2020
DOI: 10.1038/s41420-024-01854-2
ISSN: 2058-7716
PubMed: 38368399
Scopus: 2-s2.0-85185458184
Колекције
Институција/група
Tehnološko-metalurški fakultetTY - JOUR AU - Panczyszyn, Elzbieta AU - Saverio, Valentina AU - Monzani, Romina AU - Gagliardi, Mara AU - Petrović, Jelena AU - Stojkovska, Jasmina AU - Collavin, Licio AU - Corazzari, Marco PY - 2024-12 UR - http://TechnoRep.tmf.bg.ac.rs/handle/123456789/7318 AB - Human osteosarcoma (OS) is a relatively rare malignancy preferentially affecting long body bones which prognosis is often poor also due to the lack of effective therapies. Clinical management of this cancer basically relies on surgical removal of primary tumor coupled with radio/chemotherapy. Unfortunately, most osteosarcoma cells are resistant to conventional therapy, with the undergoing epithelial-mesenchymal transition (EMT) giving rise to gene expression reprogramming, thus increasing cancer cell invasiveness and metastatic potential. Alternative clinical approaches are thus urgently needed. In this context, the recently described ferroptotic cell death represents an attractive new strategy to efficiently kill cancer cells, since most chemoresistant and mesenchymal-shaped tumors display high susceptibility to pro-ferroptotic compounds. However, cancer cells have also evolved anti-ferroptotic strategies, which somehow sustain their survival upon ferroptosis induction. Indeed, here we show that osteosarcoma cell lines display heterogeneous sensitivity to ferroptosis execution, correlating with the mesenchymal phenotype, which is consistently affected by the expression of the well-known anti-ferroptotic factor ferroptosis suppressor protein 1 (FSP1). Interestingly, inhibiting the activity or expression of FSP1 restores cancer cell sensitivity to ferroptosis. Moreover, we also found that: i) AKRs might also contribute to resistance; ii) NRF2 enhances FSP1 expression upon ferroptosis induction; while iii) p53 contributes to the regulation of FSP1 basal expression in OS cells. In conclusion, FSP1 expression can potentially be used as a valuable predictive marker of OS sensitivity to ferroptosis and as a new potential therapeutic target. PB - Springer Nature T2 - Cell Death Discovery T1 - FSP1 is a predictive biomarker of osteosarcoma cells’ susceptibility to ferroptotic cell death and a potential therapeutic target IS - 1 SP - 87 VL - 10 DO - 10.1038/s41420-024-01854-2 ER -
@article{ author = "Panczyszyn, Elzbieta and Saverio, Valentina and Monzani, Romina and Gagliardi, Mara and Petrović, Jelena and Stojkovska, Jasmina and Collavin, Licio and Corazzari, Marco", year = "2024-12", abstract = "Human osteosarcoma (OS) is a relatively rare malignancy preferentially affecting long body bones which prognosis is often poor also due to the lack of effective therapies. Clinical management of this cancer basically relies on surgical removal of primary tumor coupled with radio/chemotherapy. Unfortunately, most osteosarcoma cells are resistant to conventional therapy, with the undergoing epithelial-mesenchymal transition (EMT) giving rise to gene expression reprogramming, thus increasing cancer cell invasiveness and metastatic potential. Alternative clinical approaches are thus urgently needed. In this context, the recently described ferroptotic cell death represents an attractive new strategy to efficiently kill cancer cells, since most chemoresistant and mesenchymal-shaped tumors display high susceptibility to pro-ferroptotic compounds. However, cancer cells have also evolved anti-ferroptotic strategies, which somehow sustain their survival upon ferroptosis induction. Indeed, here we show that osteosarcoma cell lines display heterogeneous sensitivity to ferroptosis execution, correlating with the mesenchymal phenotype, which is consistently affected by the expression of the well-known anti-ferroptotic factor ferroptosis suppressor protein 1 (FSP1). Interestingly, inhibiting the activity or expression of FSP1 restores cancer cell sensitivity to ferroptosis. Moreover, we also found that: i) AKRs might also contribute to resistance; ii) NRF2 enhances FSP1 expression upon ferroptosis induction; while iii) p53 contributes to the regulation of FSP1 basal expression in OS cells. In conclusion, FSP1 expression can potentially be used as a valuable predictive marker of OS sensitivity to ferroptosis and as a new potential therapeutic target.", publisher = "Springer Nature", journal = "Cell Death Discovery", title = "FSP1 is a predictive biomarker of osteosarcoma cells’ susceptibility to ferroptotic cell death and a potential therapeutic target", number = "1", pages = "87", volume = "10", doi = "10.1038/s41420-024-01854-2" }
Panczyszyn, E., Saverio, V., Monzani, R., Gagliardi, M., Petrović, J., Stojkovska, J., Collavin, L.,& Corazzari, M.. (2024-12). FSP1 is a predictive biomarker of osteosarcoma cells’ susceptibility to ferroptotic cell death and a potential therapeutic target. in Cell Death Discovery Springer Nature., 10(1), 87. https://doi.org/10.1038/s41420-024-01854-2
Panczyszyn E, Saverio V, Monzani R, Gagliardi M, Petrović J, Stojkovska J, Collavin L, Corazzari M. FSP1 is a predictive biomarker of osteosarcoma cells’ susceptibility to ferroptotic cell death and a potential therapeutic target. in Cell Death Discovery. 2024;10(1):87. doi:10.1038/s41420-024-01854-2 .
Panczyszyn, Elzbieta, Saverio, Valentina, Monzani, Romina, Gagliardi, Mara, Petrović, Jelena, Stojkovska, Jasmina, Collavin, Licio, Corazzari, Marco, "FSP1 is a predictive biomarker of osteosarcoma cells’ susceptibility to ferroptotic cell death and a potential therapeutic target" in Cell Death Discovery, 10, no. 1 (2024-12):87, https://doi.org/10.1038/s41420-024-01854-2 . .