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

Mendes, Cindy; Lopes‐Coelho, Filipa; Ramos, Cristiano; Martins, Filipa; Santos, Inês P.; Rodrigues, Armanda; Silva, Fernanda; André, Saudade; Serpa, Jacinta

doi:10.1038/s41598-019-50531-3

Cited by 20 publications

(24 citation statements)

References 55 publications

(62 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…However, when wild-type p53 fulfils its role as a tumor-suppressor, this interference may result in tumor-promoting effects. Indeed, opposite effects of ERβ have also been reported, with ERβ1 activation stimulating TNBC proliferation [50,51], promoting TNBC cell survival [52] and increasing tumor aggressiveness [50,53]. In summary, the overall effect of ERβ on prognosis of TNBC in preclinical models appears inconclusive.…”

Section: Preclinical Evidence For a Role Of Estrogen And Progesterone In Tnbc 31 Estrogen Receptor Beta In Tnbcmentioning

confidence: 99%

Estrogens and Progestogens in Triple Negative Breast Cancer: Do They Harm?

Barele

Heemskerk-Gerritsen

Louwers

et al. 2021

Cancers

View full text Add to dashboard Cite

Triple-negative breast cancers (TNBC) occur more frequently in younger women and do not express estrogen receptor (ER) nor progesterone receptor (PR), and are therefore often considered hormone-insensitive. Treatment of premenopausal TNBC patients almost always includes chemotherapy, which may lead to premature ovarian insufficiency (POI) and can severely impact quality of life. Hormone replacement therapy (HRT) is contraindicated for patients with a history of hormone-sensitive breast cancer, but the data on safety for TNBC patients is inconclusive, with a few randomized trials showing increased risk-ratios with wide confidence intervals for recurrence after HRT. Here, we review the literature on alternative pathways from the classical ER/PR. We find that for both estrogens and progestogens, potential alternatives exist for exerting their effects on TNBC, ranging from receptor conversion, to alternative receptors capable of binding estrogens, as well as paracrine pathways, such as RANK/RANKL, which can cause progestogens to indirectly stimulate growth and metastasis of TNBC. Finally, HRT may also influence other hormones, such as androgens, and their effects on TNBCs expressing androgen receptors (AR). Concluding, the assumption that TNBC is completely hormone-insensitive is incorrect. However, the direction of the effects of the alternative pathways is not always clear, and will need to be investigated further.

show abstract

Section: Preclinical Evidence For a Role Of Estrogen And Progesterone In Tnbc 31 Estrogen Receptor Beta In Tnbcmentioning

confidence: 99%

Estrogens and Progestogens in Triple Negative Breast Cancer: Do They Harm?

Barele

Heemskerk-Gerritsen

Louwers

et al. 2021

Cancers

View full text Add to dashboard Cite

show abstract

“…Their role as FA transporters and their function are still not fully clarified (54,70). FATP1 is involved in FA metabolism and cancer progression (71)(72)(73). FATPs expression is highly heterogeneous in PCa tissues and cell lines and it varies across databases and detection methodologies (64,74).…”

Section: Alterations In Fa Uptakementioning

confidence: 99%

Prostate Cancer Progression: as a Matter of Fats

2021

View full text Add to dashboard Cite

Advanced prostate cancer (PCa) represents the fifth cause of cancer death worldwide. Although survival has improved with second-generation androgen signaling and Parp inhibitors, the benefits are not long-lasting, and new therapeutic approaches are sorely needed. Lipids and their metabolism have recently reached the spotlight with accumulating evidence for their role as promoters of PCa development, progression, and metastasis. As a result, interest in targeting enzymes/transporters involved in lipid metabolism is rapidly growing. Moreover, the use of lipogenic signatures to predict prognosis and resistance to therapy has been recently explored with promising results. Despite the well-known association between obesity with PCa lethality, the underlying mechanistic role of diet/obesity-derived metabolites has only lately been unveiled. Furthermore, the role of lipids as energy source, building blocks, and signaling molecules in cancer cells has now been revisited and expanded in the context of the tumor microenvironment (TME), which is heavily influenced by the external environment and nutrient availability. Here, we describe how lipids, their enzymes, transporters, and modulators can promote PCa development and progression, and we emphasize the role of lipids in shaping TME. In a therapeutic perspective, we describe the ongoing efforts in targeting lipogenic hubs. Finally, we highlight studies supporting dietary modulation in the adjuvant setting with the purpose of achieving greater efficacy of the standard of care and of synthetic lethality. PCa progression is “a matter of fats”, and the more we understand about the role of lipids as key players in this process, the better we can develop approaches to counteract their tumor promoter activity while preserving their beneficial properties.

show abstract

“…Particularly, hepatocellular carcinoma progression was correlated with CD36/fatty acid translocase and high free fatty acid levels via induction of EMT, which was promoted by TGF-b and Wnt signaling (172). Fatty acid transport protein 1 (FATP1), a member of the FATP/SLC27 protein family, which increases the cellular uptake of long-chain fatty acids (174), has been linked to cancer progression (175) and is also likely to be involved in metastasis. Considering breast cancer patients and using data from the TCGA database, it was observed that metastases expressed higher levels of FATP1/SLC16A1 when comparing to normal breast tissue (175).…”

Section: Fatty Acid Metabolismmentioning

confidence: 99%

“…Fatty acid transport protein 1 (FATP1), a member of the FATP/SLC27 protein family, which increases the cellular uptake of long-chain fatty acids (174), has been linked to cancer progression (175) and is also likely to be involved in metastasis. Considering breast cancer patients and using data from the TCGA database, it was observed that metastases expressed higher levels of FATP1/SLC16A1 when comparing to normal breast tissue (175). In addition, in melanoma patients, the expression of FATP1 was found to be higher in subcutaneous metastases when compared to primary tumors (176).…”

Section: Fatty Acid Metabolismmentioning

confidence: 99%

“…Moreover, orlistat, an irreversible inhibitor of FASN, was shown to reduce tumor lung metastases (53.4%) in C57BL/6 mice subcutaneously injected with melanoma B16-F10 cells (223). Interrupting the mechanisms of lipid uptake through the pharmacological inhibition of FATP1 with arylpiperazines (224) represents a promising therapeutic strategy for breast cancer and melanoma, as this protein is overexpressed in these tumors (175,176). Although the effect of arylpiperazines on invasion and metastasis has not been studied yet, the inhibition of FATP1 with arylpiperazines interfered with the uptake of fatty acids and cell viability of breast cancer cells (175).…”

Section: Metabolic Targeting Encloses the Success Of The Treatment Of Metastatic Diseasementioning

confidence: 99%

See 1 more Smart Citation

Molecular and Metabolic Reprogramming: Pulling the Strings Toward Tumor Metastasis

et al. 2021

Self Cite

View full text Add to dashboard Cite

Metastasis is a major hurdle to the efficient treatment of cancer, accounting for the great majority of cancer-related deaths. Although several studies have disclosed the detailed mechanisms underlying primary tumor formation, the emergence of metastatic disease remains poorly understood. This multistep process encompasses the dissemination of cancer cells to distant organs, followed by their adaptation to foreign microenvironments and establishment in secondary tumors. During the last decades, it was discovered that these events may be favored by particular metabolic patterns, which are dependent on reprogrammed signaling pathways in cancer cells while they acquire metastatic traits. In this review, we present current knowledge of molecular mechanisms that coordinate the crosstalk between metastatic signaling and cellular metabolism. The recent findings involving the contribution of crucial metabolic pathways involved in the bioenergetics and biosynthesis control in metastatic cells are summarized. Finally, we highlight new promising metabolism-based therapeutic strategies as a putative way of impairing metastasis.

show abstract

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

Cited by 20 publications

References 55 publications

Estrogens and Progestogens in Triple Negative Breast Cancer: Do They Harm?

Estrogens and Progestogens in Triple Negative Breast Cancer: Do They Harm?

Prostate Cancer Progression: as a Matter of Fats

Molecular and Metabolic Reprogramming: Pulling the Strings Toward Tumor Metastasis

Contact Info

Product

Resources

About