Nucleo-cytoplasmic transport of estrogen receptor alpha in breast cancer cells

Tecalco-Cruz, Ángeles C.; Pérez-Alvarado, Issis A.; Ramírez-Jarquín, Josué O.; Rocha‐Zavaleta, Leticia

doi:10.1016/j.cellsig.2017.03.011

Cited by 46 publications

(52 citation statements)

References 137 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…How ETV4 is affecting ER's localization remains unclear, though it may be doing this through multiple mechanisms. ER contains both an established nuclear localization signal and two regions considered non-canonical nuclear export signals [36]. Multiple post translational modifications have been shown to affect these sites, though it is not fully understood.…”

Section: Discussionmentioning

confidence: 99%

ETV4 is necessary for estrogen signaling and growth in endometrial cancer cells

Rodriguez

Vahrenkamp

Berrett

et al. 2019

Preprint

View full text Add to dashboard Cite

Estrogen signaling through estrogen receptor alpha (ER) plays a major role in endometrial cancer risk and progression; however, the molecular mechanisms underlying ER's regulatory role in endometrial cancer are poorly understood. In breast cancer cells, ER genomic binding is enabled by FOXA1 and GATA3, but the transcription factors that control ER genomic binding in endometrial cancer cells remain unknown. We previously identified ETV4 as a candidate factor controlling ER genomic binding in endometrial cancer cells and here we explore the functional importance of ETV4. Homozygous deletion of ETV4, using CRISPR/Cas9, led to greatly reduced ER binding at the majority of loci normally bound by ER. Consistent with the dramatic loss of ER binding, the gene expression response to estradiol was dampened for most genes. ETV4 contributes to estrogen signaling in two distinct ways; ETV4 loss impacts chromatin accessibility at some ER bound loci and impairs ER nuclear translocation. The diminished estrogen signaling upon ETV4 deletion led to decreased growth, particularly in 3D culture where hollow organoids were formed and in vivo in the context of estrogen dependent growth. Our results show that ETV4 plays an important role in estrogen signaling in endometrial cancer cells.

show abstract

Section: Discussionmentioning

confidence: 99%

ETV4 is necessary for estrogen signaling and growth in endometrial cancer cells

Rodriguez

Vahrenkamp

Berrett

et al. 2019

Preprint

View full text Add to dashboard Cite

show abstract

“…Thus, we hypothesized that overexpressed Sirt3 indirectly regulates the expression of ERα in MCF-7 breast cancer cells. It is known that ERα contains a nuclear localization signal for the transport into the nucleus, which happens 10 to 30 min after E2 stimulation (reviewed by [40]). Therefore, we investigated the nuclear level of ERα as an indicator of its E2-stimulated activation.…”

Section: Discussionmentioning

confidence: 99%

Sirt3 Exerts Its Tumor-Suppressive Role by Increasing p53 and Attenuating Response to Estrogen in MCF-7 Cells

et al. 2020

View full text Add to dashboard Cite

Estrogen (E2) is a major risk factor for the initiation and progression of malignancy in estrogen receptor (ER) positive breast cancers, whereas sirtuin 3 (Sirt3), a major mitochondrial NAD+-dependent deacetylase, has the inhibitory effect on the tumorigenic properties of ER positive MCF-7 breast cancer cells. Since it is unclear if this effect is mediated through the estrogen receptor alpha (ERα) signaling pathway, in this study, we aimed to determine if the tumor-suppressive function of Sirt3 in MCF-7 cells interferes with their response to E2. Although we found that Sirt3 improves the antioxidative response and mitochondrial fitness of the MCF-7 cells, it also increases DNA damage along with p53, AIF, and ERα expression. Moreover, Sirt3 desensitizes cells to the proliferative effect of E2, affects p53 by disruption of the ERα–p53 interaction, and decreases proliferation, colony formation, and migration of the cells. Our observations indicate that these tumor-suppressive effects of Sirt3 could be reversed by E2 treatment only to a limited extent which is not sufficient to recover the tumorigenic properties of the MCF-7 cells. This study provides new and interesting insights with respect to the functional role of Sirt3 in the E2-dependent breast cancers.

show abstract

“…As reported below, ERαABs act as ERα agonists through both non-genomic and genomic procedures, which operate sequentially, the non-genomic preceding largely the genomic procedures [ 10 , 11 ]. This suspected co-operative mechanism [ 11 , 12 , 13 , 14 ], detected with MCF-7 breast cancer cells, seems to be initiated at the plasma membrane ( Section 3.2 ).…”

Section: Major Properties Of Erαabsmentioning

confidence: 99%

“… Schematic representation of ERαABs-induced mechanisms initiated at the plasma membrane to promote enhanced proliferation and ERE-dependent transcription. Reported ERαAB activities (agonism, antagonism of inhibition) were integrated in a classical model explaining co-operation between binding sites for growth factors and steroid hormones in the onset of non-genomic and genomic responses [ 11 , 12 , 14 , 27 , 33 , 37 , 38 ]. Note the pivotal role of the Ca 2+ /calmodulin complex in the inter-relationships between GPR30 and recruitment sites of the receptor for ERαABs and adjacent co-activators.…”

Section: Figurementioning

confidence: 99%

Natural Anti-Estrogen Receptor Alpha Antibodies Able to Induce Estrogenic Responses in Breast Cancer Cells: Hypotheses Concerning Their Mechanisms of Action and Emergence

Leclercq

2018

IJMS

View full text Add to dashboard Cite

The detection of human anti-estrogen receptor α antibodies (ERαABs) inducing estrogenic responses in MCF-7 mammary tumor cells suggests their implication in breast cancer emergence and/or evolution. A recent report revealing a correlation between the titer of such antibodies in sera from patients suffering from this disease and the percentage of proliferative cells in samples taken from their tumors supports this concept. Complementary evidence of the ability of ERαABs to interact with an epitope localized within the estradiol-binding core of ERα also argues in its favor. This epitope is indeed inserted in a regulatory platform implicated in ERα-initiated signal transduction pathways and transcriptions. According to some experimental observations, two auto-immune reactions may already be advocated to explain the emergence of ERαABs: one involving probably the idiotypic network to produce antibodies acting as estrogenic secretions and the other based on antibodies able to abrogate the action of a natural ERα inhibitor or to prevent the competitive inhibitory potency of released receptor degradation products able to entrap circulating estrogens and co-activators. All of this information, the aspect of which is mainly fundamental, may open new ways in the current tendency to combine immunological and endocrine approaches for the management of breast cancer.

show abstract

Nucleo-cytoplasmic transport of estrogen receptor alpha in breast cancer cells

Cited by 46 publications

References 137 publications

ETV4 is necessary for estrogen signaling and growth in endometrial cancer cells

ETV4 is necessary for estrogen signaling and growth in endometrial cancer cells

Sirt3 Exerts Its Tumor-Suppressive Role by Increasing p53 and Attenuating Response to Estrogen in MCF-7 Cells

Natural Anti-Estrogen Receptor Alpha Antibodies Able to Induce Estrogenic Responses in Breast Cancer Cells: Hypotheses Concerning Their Mechanisms of Action and Emergence

Contact Info

Product

Resources

About