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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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Autores principales: Nisticò, Clelia, Pagliari, Francesca, Chiarella, Emanuela, Fernandes Guerreiro, Joana, Marafioti, Maria Grazia, Aversa, Ilenia, Genard, Geraldine, Hanley, Rachel, Garcia-Calderón, Daniel, Bond, Heather Mandy, Mesuraca, Maria, Tirinato, Luca, Spadea, Maria Francesca, Seco, Joao Carlos
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8466244/
https://www.ncbi.nlm.nih.gov/pubmed/34576263
http://dx.doi.org/10.3390/ijms221810102
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author Nisticò, Clelia
Pagliari, Francesca
Chiarella, Emanuela
Fernandes Guerreiro, Joana
Marafioti, Maria Grazia
Aversa, Ilenia
Genard, Geraldine
Hanley, Rachel
Garcia-Calderón, Daniel
Bond, Heather Mandy
Mesuraca, Maria
Tirinato, Luca
Spadea, Maria Francesca
Seco, Joao Carlos
author_facet Nisticò, Clelia
Pagliari, Francesca
Chiarella, Emanuela
Fernandes Guerreiro, Joana
Marafioti, Maria Grazia
Aversa, Ilenia
Genard, Geraldine
Hanley, Rachel
Garcia-Calderón, Daniel
Bond, Heather Mandy
Mesuraca, Maria
Tirinato, Luca
Spadea, Maria Francesca
Seco, Joao Carlos
author_sort Nisticò, Clelia
collection PubMed
description 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.
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spelling pubmed-84662442021-09-27 Lipid Droplet Biosynthesis Impairment through DGAT2 Inhibition Sensitizes MCF7 Breast Cancer Cells to Radiation Nisticò, Clelia Pagliari, Francesca Chiarella, Emanuela Fernandes Guerreiro, Joana Marafioti, Maria Grazia Aversa, Ilenia Genard, Geraldine Hanley, Rachel Garcia-Calderón, Daniel Bond, Heather Mandy Mesuraca, Maria Tirinato, Luca Spadea, Maria Francesca Seco, Joao Carlos Int J Mol Sci Article 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. MDPI 2021-09-18 /pmc/articles/PMC8466244/ /pubmed/34576263 http://dx.doi.org/10.3390/ijms221810102 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Nisticò, Clelia
Pagliari, Francesca
Chiarella, Emanuela
Fernandes Guerreiro, Joana
Marafioti, Maria Grazia
Aversa, Ilenia
Genard, Geraldine
Hanley, Rachel
Garcia-Calderón, Daniel
Bond, Heather Mandy
Mesuraca, Maria
Tirinato, Luca
Spadea, Maria Francesca
Seco, Joao Carlos
Lipid Droplet Biosynthesis Impairment through DGAT2 Inhibition Sensitizes MCF7 Breast Cancer Cells to Radiation
title Lipid Droplet Biosynthesis Impairment through DGAT2 Inhibition Sensitizes MCF7 Breast Cancer Cells to Radiation
title_full Lipid Droplet Biosynthesis Impairment through DGAT2 Inhibition Sensitizes MCF7 Breast Cancer Cells to Radiation
title_fullStr Lipid Droplet Biosynthesis Impairment through DGAT2 Inhibition Sensitizes MCF7 Breast Cancer Cells to Radiation
title_full_unstemmed Lipid Droplet Biosynthesis Impairment through DGAT2 Inhibition Sensitizes MCF7 Breast Cancer Cells to Radiation
title_short Lipid Droplet Biosynthesis Impairment through DGAT2 Inhibition Sensitizes MCF7 Breast Cancer Cells to Radiation
title_sort lipid droplet biosynthesis impairment through dgat2 inhibition sensitizes mcf7 breast cancer cells to radiation
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8466244/
https://www.ncbi.nlm.nih.gov/pubmed/34576263
http://dx.doi.org/10.3390/ijms221810102
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