Tricyclic antidepressant amitriptyline inhibits autophagic flux and prevents tube formation in vascular endothelial cells.

Amitriptyline is a tricyclic antidepressant and an inhibitor of lysosomal acid sphingomyelinase (ASM). Amitriptyline is well known for its cardiovascular side effects and toxicity in psychiatric patients. However, the mechanisms underlying the cardiovascular side effects of amitriptyline remain largely undefined.

Correction: The atypical ubiquitin ligase RNF31 stabilizes estrogen receptor α and modulates estrogen-stimulated breast cancer cell proliferation.

Since the publication of the above article, the authors have noted that the input data in Fig. 6E is incorrect. The correct data are included in the below Fig.

Estrogen Receptor Beta-Mediated Modulation of Lung Cancer Cell Proliferation by 27-Hydroxycholesterol.

27-hydroxycholesterol (27HC) is an abundant cholesterol metabolite in human circulation and promotes breast cancer cell proliferation. Although lung is one of the organs that contain high levels of 27HC, the role of 27HC in lung is unknown. In this study, we found that 27HC promotes lung cancer cell proliferation in an estrogen receptor β (ERβ)-dependent manner.

Combining mouse embryonic stem cells and zebrafish embryos to evaluate developmental toxicity of chemical exposure.

The assays in this study utilize mouse embryonic stem cells (mESCs) and zebrafish embryos to evaluate the potential developmental toxicity of industrial and pharmaceutical chemicals. A set of eleven chemicals of known mammalian in vivo teratogenicity were tested in the assays and correlations to mammalian data. Using mESCs, proliferation, differentiation, and cytotoxicity of the chemicals were measured.

ERβ alters the chemosensitivity of luminal breast cancer cells by regulating p53 function.

Estrogen receptor α (ERα)-positive breast cancers tend to develop resistance to both endocrine therapy and chemotherapy. Despite recent progress in defining molecular pathways that confer endocrine resistance, the mechanisms that regulate chemotherapy response in luminal tumors remain largely elusive. Luminal tumors often express wild-type p53 that is a major determinant of the cellular DNA damage response.

Comparison of infectivity and spread between HSV-1 and HSV-2 based oncolytic viruses on tumor cells with different receptor expression profiles.

Herpes simplex virus (HSV) is one of the many viruses that have been modified or adapted for oncolytic purposes. There are two serotypes of HSV, HSV-1 and HSV-2. The majority of oncolytic HSVs, including T-VEC which has recently been approved by the US Food and Drug Administration (FDA) for clinical use in treating late stage melanoma patients, are derived from HSV-1.

Estrogen receptor β controls proliferation of enteric glia and differentiation of neurons in the myenteric plexus after damage.

Injury to the enteric nervous system (ENS) can cause several gastrointestinal (GI) disorders including achalasia, irritable bowel syndrome, and gastroparesis. Recently, a subpopulation of enteric glial cells with neuronal stem/progenitor properties (ENSCs) has been identified in the adult ENS. ENSCs have the ability of reconstituting the enteric neuronal pool after damage of the myenteric plexus.

Farnesoid X receptor is essential for the survival of renal medullary collecting duct cells under hypertonic stress.

Hypertonicity in renal medulla is critical for the kidney to produce concentrated urine. Renal medullary cells have to survive high medullary osmolarity during antidiuresis. Previous study reported that farnesoid X receptor (FXR), a nuclear receptor transcription factor activated by endogenous bile acids, increases urine concentrating ability by up-regulating aquaporin 2 expression in medullary collecting duct cells (MCDs).

Human Proislet Peptide Promotes Pancreatic Progenitor Cells to Ameliorate Diabetes Through FOXO1/Menin-Mediated Epigenetic Regulation.

We investigated how human proislet peptide (HIP) regulates differentiation of human fetus-derived pancreatic progenitor cells (HFPPCs) and explored the potential link between HIP signaling and the menin pathway, which is key to regulating pancreatic islet differentiation. The data show that HIP promoted expression of proislet transcription factors (TFs), including PDX-1, MAFA, and NKX6.1, as well as other maturation markers of β-cells, such as insulin, GLUT2, KIR6.

Delineation of the androgen-regulated signaling pathways in prostate cancer facilitates the development of novel therapeutic approaches.

Although androgen deprivation therapy (ADT) is initially effective for the treatment of progressive prostate cancer, it inevitably fails due to the onset of diverse resistance mechanisms that restore androgen receptor (AR) signaling. Thus, AR remains a desired therapeutic target even in the relapsed stages of the disease. Given the difficulties in stopping all AR reactivation mechanisms, we propose that the identification of the driver signaling events downstream of the receptor offer viable, alternative therapeutic targets.

Pharmacological activation of estrogen receptor beta augments innate immunity to suppress cancer metastasis.

Metastases constitute the greatest causes of deaths from cancer. However, no effective therapeutic options currently exist for cancer patients with metastasis. Estrogen receptor β (ERβ), as a member of the nuclear receptor superfamily, shows potent tumor-suppressive activities in many cancers.

The ERβ4 variant induces transformation of the normal breast mammary epithelial cell line MCF-10A; the ERβ variants ERβ2 and ERβ5 increase aggressiveness of TNBC by regulation of hypoxic signaling.

Triple negative breast cancer (TNBC) still remains a challenge to treat in the clinic due to a lack of good targets for treatment. Although TNBC lacks expression of ERα, the expression of ERβ and its variants are detected quite frequently in this cancer type and can represent an avenue for treatment. We show that two of the variants of ERβ, namely ERβ2 and ERβ5, control aggressiveness of TNBC by regulating hypoxic signaling through stabilization of HIF-1α.

Epithelial oestrogen receptor α is dispensable for the development of oestrogen-induced cervical neoplastic diseases.

Human papillomavirus (HPV) is required but not sufficient for cervical carcinoma (CxCa) development. Oestradiol (E ) promotes CxCa development in K14E7 transgenic mice expressing the HPV16 E7 oncoprotein under the control of the keratin (K14) promoter. E mainly functions through oestrogen receptor α (ERα).

Author Correction: Molecular mechanisms involved in the non-monotonic effect of bisphenol-a on Ca entry in mouse pancreatic β-cells.

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has been fixed in the paper.

Liver X receptor β regulates the development of the dentate gyrus and autistic-like behavior in the mouse.

The dentate gyrus (DG) of the hippocampus is a laminated brain region in which neurogenesis begins during early embryonic development and continues until adulthood. Recent studies have implicated that defects in the neurogenesis of the DG seem to be involved in the genesis of autism spectrum disorders (ASD)-like behaviors. Liver X receptor β (LXRβ) has recently emerged as an important transcription factor involved in the development of laminated CNS structures, but little is known about its role in the development of the DG.

GLUT12 promotes prostate cancer cell growth and is regulated by androgens and CaMKK2 signaling.

Despite altered metabolism being an accepted hallmark of cancer, it is still not completely understood which signaling pathways regulate these processes. Given the central role of androgen receptor (AR) signaling in prostate cancer, we hypothesized that AR could promote prostate cancer cell growth in part through increasing glucose uptake via the expression of distinct glucose transporters. Here, we determined that AR directly increased the expression of , the gene that encodes the glucose transporter GLUT12.

Phosphaplatin Anti-tumor Effect Enhanced by Liposomes Partly an Up-regulation of PEDF in Breast Cancer.

Background/aim: Phosphaplatin platinum (IV) (RRD4) complex has exceptional antitumor properties. The aim of this study was to investigate the effects and the mechanism of action of free and liposome-encapsulated RRD4 in breast cancer.

Materials And Methods: Liposome-encapsulated RRD4 prepared by thin-film dehydration: hydration and free RRD4 were tested in vivo and in vitro against 4T1 breast cancer cells.

Body weight homeostat that regulates fat mass independently of leptin in rats and mice.

Subjects spending much time sitting have increased risk of obesity but the mechanism for the antiobesity effect of standing is unknown. We hypothesized that there is a homeostatic regulation of body weight. We demonstrate that increased loading of rodents, achieved using capsules with different weights implanted in the abdomen or s.

Deep mutational scanning of S. pyogenes Cas9 reveals important functional domains.

RNA-guided endonucleases (RGENs) have invigorated the field of site-specific nucleases. The success of Streptococcus pyogenes Cas9 (SpCas9) has led to the discovery of several other CRISPR-associated RGENs. As more RGENs become available, it will be necessary to refine their activity before they can be translated into the clinic.

Communication between genomic and non-genomic signaling events coordinate steroid hormone actions.

Steroid hormones are lipophilic molecules produced in one cell that can travel great distances within the body to elicit biological effects in another cell. In the canonical pathway, steroid hormone binding to a nuclear receptor (NR), often in the cytoplasm, causes the receptor to undergo a conformational change and translocate to the nucleus, where it interacts with specific sequences of DNA to regulate transcription. In addition to the classical genomic mechanism of action, alternate mechanisms of steroid activity have emerged that involve rapid, non-genomic signaling.

Role of estrogen receptor beta in neural differentiation of mouse embryonic stem cells.

The ability to propagate mature cells and tissue from pluripotent stem cells offers enormous promise for treating many diseases, including neurodegenerative diseases. Before such cells can be used successfully in neurodegenerative diseases without causing unwanted cell growth and migration, genes regulating growth and migration of neural stem cells need to be well characterized. Estrogen receptor beta (ERβ) is essential for migration of neurons and glial cells in the developing mouse brain.

ERβ Sensitizes NSCLC to Chemotherapy by Regulating DNA Damage Response.

The expression of wild-type estrogen receptor β (ESR2/ERβ1) correlates with clinical outcome in patients with non-small cell lung cancer (NSCLC). However, the molecular mechanism that accounts for this association is currently poorly understood. ERβ1 was previously linked to chemotherapy response in patients with breast cancer and in breast cancer cells.

Estrogen receptor β2 induces proliferation and invasiveness of triple negative breast cancer cells: association with regulation of PHD3 and HIF-1α.

The two estrogen receptor (ER) subtypes, ERα and ERβ, belong to the nuclear receptor superfamily. The human ERβ variant ERβ2 is proposed to be expressed at higher levels than ERβ1 in many breast tumors and it has been suggested that ERβ2, in contrast to ERβ1, is associated with aggressive phenotypes of various cancers. However, the role of endogenous ERβ2 in breast cancer cells remains elusive.

Genetically tunable frustration controls allostery in an intrinsically disordered transcription factor.

Intrinsically disordered proteins (IDPs) present a functional paradox because they lack stable tertiary structure, but nonetheless play a central role in signaling, utilizing a process known as allostery. Historically, allostery in structured proteins has been interpreted in terms of propagated structural changes that are induced by effector binding. Thus, it is not clear how IDPs, lacking such well-defined structures, can allosterically affect function.