Unraveling FATP1, regulated by ER-β, as a targeted breast cancer innovative therapy

Cindy Mendes, Filipa Lopes-Coelho, Cristiano Ramos, Filipa Martins, Inês Santos, Armanda Rodrigues, Fernanda Silva, Saudade André, Jacinta Serpa

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Abstract

The biochemical demands associated with tumor proliferation prompt neoplastic cells to augment the import of nutrients to sustain their survival and fuel cell growth, with a consequent metabolic remodeling. Fatty acids (FA) are crucial in this process, since they have a dual role as energetic coins and building blocks. Recently, our team has shown that FATP1 has a pivotal role in FA transfer between breast cancer cells (BCCs) and non-cancerous cells in the microenvironment. We aimed to investigate the role of FATP1 in BCCs and also to explore if FATP1 inhibition is a promising therapeutic strategy. In patients' data, we showed a higher expression of FATP1/SLC27A1 in TNBC, which correlated with a significant decreased overall survival (OS). In vitro, we verified that FA and estradiol stimulated FATP1/SLC27A1 expression in BCCs. Additionally, experiments with estradiol and PHTPP (ER-β antagonist) showed that estrogen receptor-β (ER-β) regulates FATP1/SLC27A1 expression, the uptake of FA and cell viability, in four BCC lines. Furthermore, the inhibition of FATP1 with arylpiperazine 5k (DS22420314) interfered with the uptake of FA and cell viability. Our study, unraveled FATP1 as a putative therapeutic target in breast cancer (BC).

Original languageEnglish
Number of pages1
JournalScientific Reports
Volume9
Issue number1
DOIs
Publication statusPublished - 1 Oct 2019

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Investigational Therapies
Estrogen Receptors
Fatty Acids
Breast Neoplasms
Cell Survival
Estradiol
Cellular Microenvironment
Numismatics
Cell Line
Food
Survival
Therapeutics
Growth
Neoplasms

Cite this

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title = "Unraveling FATP1, regulated by ER-β, as a targeted breast cancer innovative therapy",
abstract = "The biochemical demands associated with tumor proliferation prompt neoplastic cells to augment the import of nutrients to sustain their survival and fuel cell growth, with a consequent metabolic remodeling. Fatty acids (FA) are crucial in this process, since they have a dual role as energetic coins and building blocks. Recently, our team has shown that FATP1 has a pivotal role in FA transfer between breast cancer cells (BCCs) and non-cancerous cells in the microenvironment. We aimed to investigate the role of FATP1 in BCCs and also to explore if FATP1 inhibition is a promising therapeutic strategy. In patients' data, we showed a higher expression of FATP1/SLC27A1 in TNBC, which correlated with a significant decreased overall survival (OS). In vitro, we verified that FA and estradiol stimulated FATP1/SLC27A1 expression in BCCs. Additionally, experiments with estradiol and PHTPP (ER-β antagonist) showed that estrogen receptor-β (ER-β) regulates FATP1/SLC27A1 expression, the uptake of FA and cell viability, in four BCC lines. Furthermore, the inhibition of FATP1 with arylpiperazine 5k (DS22420314) interfered with the uptake of FA and cell viability. Our study, unraveled FATP1 as a putative therapeutic target in breast cancer (BC).",
author = "Cindy Mendes and Filipa Lopes-Coelho and Cristiano Ramos and Filipa Martins and In{\^e}s Santos and Armanda Rodrigues and Fernanda Silva and Saudade Andr{\'e} and Jacinta Serpa",
note = "The authors thank to Shinozuka Tsuyoshi from Daiichi Sankyo, Japan, for the supply of arylpiperazine 5k (DS22420314). The research was funded by IPOLFG, EPE (FAI 2017) and by iNOVA4Health - UID/Multi/04462/a program fnancially supported by Funda{\cc}{\~a}o para a Ci{\^e}ncia e Tecnologia/Minist{\'e}rio da Educa{\cc}{\~a}o e Ci{\^e}ncia, through national funds and co-funded by FEDER under the PT2020 Partnership Agreement and by Funda{\cc}{\~a}o para a Ci{\^e}ncia e Tecnologia (personal fellowship: PD/BD/128337/2017).",
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Unraveling FATP1, regulated by ER-β, as a targeted breast cancer innovative therapy. / Mendes, Cindy; Lopes-Coelho, Filipa; Ramos, Cristiano; Martins, Filipa; Santos, Inês; Rodrigues, Armanda; Silva, Fernanda; André, Saudade; Serpa, Jacinta.

In: Scientific Reports, Vol. 9, No. 1, 01.10.2019.

Research output: Contribution to journalArticle

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AU - Rodrigues, Armanda

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AU - André, Saudade

AU - Serpa, Jacinta

N1 - The authors thank to Shinozuka Tsuyoshi from Daiichi Sankyo, Japan, for the supply of arylpiperazine 5k (DS22420314). The research was funded by IPOLFG, EPE (FAI 2017) and by iNOVA4Health - UID/Multi/04462/a program fnancially supported by Fundação para a Ciência e Tecnologia/Ministério da Educação e Ciência, through national funds and co-funded by FEDER under the PT2020 Partnership Agreement and by Fundação para a Ciência e Tecnologia (personal fellowship: PD/BD/128337/2017).

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