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Lipid droplet biosynthesis impairment through dgat2 inhibition sensitizes mcf7 breast cancer cells to radiation

Breast cancer is the most frequent cancer in women worldwide and late diagnosis often adversely affects the prognosis of the disease. Radiotherapy is commonly used to treat breast cancer, reducing the risk of recurrence after surgery. However, the eradication of radioresistant cancer cells, includin...

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Main Authors: Nisticò, Clelia (Author) , Pagliari, Francesca (Author) , Chiarella, Emanuela (Author) , Fernandes Guerreiro, Joana (Author) , Marafioti, Maria Grazia (Author) , Aversa, Ilenia (Author) , Genard, Geraldine (Author) , Hanley, Rachel (Author) , Garcia-Calderón, Daniel (Author) , Bond, Heather Mandy (Author) , Mesuraca, Maria (Author) , Tirinato, Luca (Author) , Spadea, Maria Francesca (Author) , Seco, Joao (Author)
Format: Article (Journal)
Language:English
Published: 18 September 2021
In: International journal of molecular sciences
Year: 2021, Volume: 22, Issue: 18, Pages: 1-18
ISSN:1422-0067
DOI:10.3390/ijms221810102
Online Access:Verlag, kostenfrei, Volltext: https://doi.org/10.3390/ijms221810102
Verlag, kostenfrei, Volltext: https://www.mdpi.com/1422-0067/22/18/10102
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Author Notes:Clelia Nisticò, Francesca Pagliari, Emanuela Chiarella, Joana Fernandes Guerreiro, Maria Grazia Marafioti, Ilenia Aversa, Geraldine Genard, Rachel Hanley, Daniel Garcia-Calderón, Heather Mandy Bond, Maria Mesuraca, Luca Tirinato, Maria Francesca Spadea and Joao Carlos Seco
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Summary:Breast cancer is the most frequent cancer in women worldwide and late diagnosis often adversely affects the prognosis of the disease. Radiotherapy is commonly used to treat breast cancer, reducing the risk of recurrence after surgery. However, the eradication of radioresistant cancer cells, including cancer stem cells, remains the main challenge of radiotherapy. Recently, lipid droplets (LDs) have been proposed as functional markers of cancer stem cells, also being involved in increased cell tumorigenicity. LD biogenesis is a multistep process requiring various enzymes, including Diacylglycerol acyltransferase 2 (DGAT2). In this context, we evaluated the effect of PF-06424439, a selective DGAT2 inhibitor, on MCF7 breast cancer cells exposed to X-rays. Our results demonstrated that 72 h of PF-06424439 treatment reduced LD content and inhibited cell migration, without affecting cell proliferation. Interestingly, PF-06424439 pre-treatment followed by radiation was able to enhance radiosensitivity of MCF7 cells. In addition, the combined treatment negatively interfered with lipid metabolism-related genes, as well as with EMT gene expression, and modulated the expression of typical markers associated with the CSC-like phenotype. These findings suggest that PF-06424439 pre-treatment coupled to X-ray exposure might potentiate breast cancer cell radiosensitivity and potentially improve the radiotherapy effectiveness.
Item Description:Published 18 September 2021
Gesehen am 21.02.2022
Physical Description:Online Resource
ISSN:1422-0067
DOI:10.3390/ijms221810102

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