Nongenomic actions of steroid hormones

Lösel, Ralf; Wehling, Martin

doi:10.1038/nrm1009

Cited by 807 publications

(557 citation statements)

References 111 publications

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“…We showed that estrogen rapidly induces c-Src activation via phosphorylation of Tyr 416, leading to the formation of the p-Src/ZO-1 complex at the cell membrane. This finding was consistent with previous reports showing that, in addition to its nuclear functions, ER also participates in extranuclear signaling events [30]. These events include the binding of ER beta to c-Src in prostate cancer cells [31]; the ER-Src axis constitutes a critical pathway used by breast cancer cells in the development of resistance [10].…”

Section: Discussionsupporting

confidence: 93%

Membrane-Initiated Estradiol Signaling of Epithelial-Mesenchymal Transition-Associated Mechanisms Through Regulation of Tight Junctions in Human Breast Cancer Cells

et al. 2014

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Tumor cells utilize inappropriate epithelialmesenchymal transition (EMT) mechanisms during the invasive process. It is becoming increasingly clear that estradiol (E2) induces breast cancer cell progression and enhances EMT; however, the mechanisms associated with this are unclear. We investigated the role of E2 on the expression and intracellular localization of the tight junction (TJ)-associated proteins, zonula occluden 1 (ZO-1), ZO-1-associated nucleic acid binding (ZONAB), and occludin, on the activation of cSrc and human epidermal growth factor receptor 2 (HER2) expression and cellular migration in the estrogen receptor (ER)-positive breast cancer cell lines, MCF-7 and T47D. WeNovelty and Impact Statements We demonstrated that estrogen is able to induce tight junction (TJ) disruption in two breast cancer cell lines through the activation of c-Src. Ablated expression of the novel epithelial marker CRB3 could lead to increased cell migration. Based on our findings, we propose a novel estrogen-induced TJ pathway associated with breast cancer cell motility and, eventually, to metastasis. demonstrated that 1 nM E2 elicits c-Src activation after 15 min. The p-Src/ZO-1 complex led to ZO-1 and ZONAB disruption at the TJ and increased expression of HER2 mRNAs. These changes correlate with decreased expression of the epithelial markers occludin and CRB3 and increased synthesis of N-cadherin. This led to increased MCF-7 cell migration induced by E2, even in the presence of a cell proliferation inhibitor. Incubation with ICI 182,780 (Fulvestrant), an ER antagonist, precluded the effects of E2 on c-Src phosphorylation, p-Src/ZO-1 complex formation, ZO-1/ZONAB nuclear translocation, and migration of MCF-7 cells. Our findings suggest that E2 promotes TJ disruption during tumor progression and increases cell motility. We propose a novel pathway where estrogens promote EMTassociated mechanisms that possibly lead to metastasis.

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Section: Discussionsupporting

confidence: 93%

Membrane-Initiated Estradiol Signaling of Epithelial-Mesenchymal Transition-Associated Mechanisms Through Regulation of Tight Junctions in Human Breast Cancer Cells

et al. 2014

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“…The extracellular application of progesterone also rapidly triggers hyperactivated motility and initiation of the acrosome reaction [84][85][86][87][88][89][90][91]. Based on the fast activation rate, and fact that sperm cells are transcriptionally silent, it was believed that the nuclear progesterone receptor was not involved [85,88,[92][93][94][95]. However, direct evidence of the instantaneous, and therefore non-genomic, effect of this steroid only came with the discovery that progesterone acts on human sperm through potentiation of the CatSper channel [18,27] with EC 50 ∼ 7 nM [18].…”

Section: Calcium Channels and Hyperactivationmentioning

confidence: 99%

Flagellar ion channels of sperm: similarities and differences between species

et al. 2015

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a b s t r a c tMotility and fertilization potential of mammalian sperm are regulated by ion homeostasis which in turn is under tight control of ion channels and transporters. Sperm intracellular pH, membrane voltage and calcium concentration ([Ca 2+ ] i ) are all important for sperm activity within the female reproductive tract. While all mammalian sperm are united in their goal to find and fertilize an egg, the molecular mechanisms they utilize for this purpose are diverse and differ between species especially on the level of ion channels. Recent direct recording from sperm cells of different species indicate the differences between rodent, non-human primate, ruminant, and human sperm on the basic levels of their ion channel regulation. In this review we summarize the current knowledge about ion channel diversity of the animal kingdom and concentrate our attention on flagellar ion channels of mammalian sperm.

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“…Alternate mechanisms have been proposed that rely on short-term, rapid cytoplasmic-based signaling effect initiated from the steroid receptor known as nonclassical or nongenomic steroid signals [11]. Nongenomic steroid signaling responses tend to be rapid, insensitive to inhibitors of mRNA and protein synthesis, lack nuclear-based steroid receptors, can be initiated by steroids coupled with high molecular weight substances such as estrogen-bovine serum albumin that do not permit transition across the plasma membrane, and are located in highly specialized cells (e.g., spermatozoa) that do not require mRNA and protein synthesis.…”

Section: Estrogen Signalingmentioning

confidence: 99%

RETRACTED ARTICLE: Regulation of estrogen receptor signaling in breast carcinogenesis and breast cancer therapy

Zhou

Qiao

Shetty

et al. 2013

Cell. Mol. Life Sci.

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Estrogen and estrogen receptors (ERs) are critical regulators of breast epithelial cell proliferation, differentiation, and apoptosis. Compromised signaling vis-à-vis the estrogen receptor is believed © Springer Basel 2013 yow4@pitt.edu. ), which predicts for response to endocrine-based therapy; however, innate or acquired resistance to endocrinebased drugs remains a serious challenge. The complexity of regulation for estrogen signaling coupled with the crosstalk of other oncogenic signaling pathways is a reason for endocrine therapy resistance. Alternative strategies that target novel molecular mechanisms are necessary to overcome this current and urgent gap in therapy. A thorough analysis of estrogen-signaling regulation is critical. In this review article, we will summarize current insights into the regulation of estrogen signaling as related to breast carcinogenesis and breast cancer therapy. NIH Public Access

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Nongenomic actions of steroid hormones

Cited by 807 publications

References 111 publications

Membrane-Initiated Estradiol Signaling of Epithelial-Mesenchymal Transition-Associated Mechanisms Through Regulation of Tight Junctions in Human Breast Cancer Cells

Membrane-Initiated Estradiol Signaling of Epithelial-Mesenchymal Transition-Associated Mechanisms Through Regulation of Tight Junctions in Human Breast Cancer Cells

Flagellar ion channels of sperm: similarities and differences between species

RETRACTED ARTICLE: Regulation of estrogen receptor signaling in breast carcinogenesis and breast cancer therapy

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