Steroid sulfatase suppresses keratinization by inducing proteasomal degradation of E-cadherin via Hakai regulation.

X-linked ichthyosis (XLI) is a genetic disorder characterized by a steroid sulfatase (STS) deficiency inducing excessive cholesterol sulfate accumulation and keratinization. Our study utilizes STS knockout mice to reproduce the hyperkeratinization typical of XLI, providing a valuable model for investigating the underlying mechanisms. From the experiment of STS-deficient keratinocytes using the CRISPR/Cas9 system, we observed upregulation of E-cadherin, which is associated with keratinocyte differentiation and stratification.

Upregulation of YPEL3 expression and induction of human breast cancer cell death by microRNAs.

Unlabelled: MicroRNAs (miRNAs), molecules comprising 18-22 nucleotides, regulate expression of genes post-transcriptionally at the 3' untranslated region of target mRNAs. However, the biological roles and mechanisms of action of miRNAs in breast cancer remain unelucidated. Thus, in this study, we aimed to investigate the functions and possible mechanisms of action of miRNAs in breast cancer to suppress carcinogenesis.

Correction: Upregulation of YPEL3 expression and induction of human breast cancer cell death by microRNAs.

[This corrects the article DOI: 10.1007/s43188-024-00251-2.].

Unraveling the molecular mechanisms of cell migration impairment and apoptosis associated with steroid sulfatase deficiency: Implications for X-linked ichthyosis.

Steroid sulfatase (STS) deficiency is responsible for X-linked ichthyosis (XLI), a genetic disorder characterized by rough and dry skin caused by excessive keratinization. The impaired keratinization process leads to reduced cell mobility and increased apoptosis, which can cause an excessive buildup of the stratum corneum. In this study, we investigated the mechanisms underlying XLI and found that STS deficiency reduces cell mobility and increases apoptosis in human keratinocyte HaCaT cells.

YPEL3 expression induces cellular senescence via the Hippo signaling pathway in human breast cancer cells.

The Hippo pathway is a signaling pathway that controls organ size in animals by regulating cell proliferation and apoptosis. Yes-associated protein 1 (YAP1), an oncogene associated with the development and progression of breast cancer, is downregulated by the Hippo pathway and is associated with the development and progression of breast cancer. Yippee-like 3 (YPEL3) is a target gene of the tumor suppressor protein p53, and its activation has been shown to inhibit cell growth, induce cellular senescence, and suppress tumor cell metastasis.

Enhancing the invasive traits of breast cancers by CYP1B1 via regulation of p53 to promote uPAR expression.

Human cytochrome P450 1B1 (CYP1B1) catalyzes estrogen metabolism to produce metabolites that promote the progression of breast cancer. Since the invasive properties of cancer cells cause cancer relapse, which dramatically reduces patient survival, we investigated the new pro-invasive mechanism involving CYP1B1 in breast cancer. Exploring clinical data from invasive breast cancer patients revealed that CYP1B1 exhibits a potential correlation with urokinase-type plasminogen activator receptor (uPAR).

Induction of synergistic apoptosis by tetramethoxystilbene and nutlin-3a in human cervical cancer cells.

2,4,3',5'-Tetramethoxystilbene (TMS) is a selective inhibitor of cytochrome P450 1B1 to block the conversion from estradiol to 4-OH-estradiol. Several studies suggested that TMS may act as a potent anti-cancer agent for hormone-related cancer including cervical cancer. Nutlin-3a is a cis-imidazoline analog that interferes with the interaction between mouse double minute 2 homolog (MDM2) and the tumor suppressor p53.

Anticancer activity and metabolic profile alterations by ortho-topolin riboside in in vitro and in vivo models of non-small cell lung cancer.

Lung cancer has the highest incidence and mortality rates among all types of cancer worldwide, and 80%-85% of patients with lung cancer are diagnosed with non-small cell lung cancer (NSCLC), which has 5-year survival rate of only 5% at advanced stages. Development of new therapeutic agents and strategies is required to enhance the treatment efficiency in patients with NSCLC. Metabolic alterations and anticancer effects of plant hormones and their derivatives have not been investigated in NSCLC in vitro and in vivo.

Steroid sulfatase deficiency causes cellular senescence and abnormal differentiation by inducing Yippee-like 3 expression in human keratinocytes.

Human steroid sulfatase (STS) is an enzyme that catalyzes the hydrolysis of dehydroepiandrosterone sulfate (DHEAS), estrone sulfate (E1S), and cholesterol sulfate. Abnormal expression of STS causes several diseases including colorectal, breast, and prostate cancer and refractory skin disease. In particular, accumulation of intracellular cholesterol sulfate by STS deficiency leads to a skin disorder with abnormal keratinization called X-linked ichthyosis (XLI).

CCL8 mediates crosstalk between endothelial colony forming cells and triple-negative breast cancer cells through IL-8, aggravating invasion and tumorigenicity.

Triple-negative breast cancer (TNBC) is an aggressive type of breast cancer with a poor prognosis for which no effective therapeutic measures are currently available. The present study aimed to investigate whether interactions with endothelial colony-forming cells (ECFCs) promote aggressive progression of TNBC cells. Herein, using an indirect co-culture system, we showed that co-culture increased the invasive and migratory phenotypes of both MDA-MB-231 TNBC cells and ECFCs.

Biological roles of cytochrome P450 1A1, 1A2, and 1B1 enzymes.

Human cytochrome P450 enzymes (CYPs) play a critical role in various biological processes and human diseases. CYP1 family members, including CYP1A1, CYP1A2, and CYP1B1, are induced by aryl hydrocarbon receptors (AhRs). The binding of ligands such as polycyclic aromatic hydrocarbons activates the AhRs, which are involved in the metabolism (including oxidation) of various endogenous or exogenous substrates.

Combined treatment with auranofin and trametinib induces synergistic apoptosis in breast cancer cells.

Auranofin is a gold complex used as an anti-rheumatic agent and may act as a potent anticancer drug against breast tumors. Trametinib is a specific mitogen-activated protein kinase inhibitor, approved for the treatment of metastatic melanoma. The aim of this study was to examine the synergistic effects of auranofin and trametinib on apoptosis in MCF-7 human breast cancer cells.

Synergistic Induction of Apoptosis by the Combination of an Axl Inhibitor and Auranofin in Human Breast Cancer Cells.

Axl receptor tyrosine kinase has been implicated in cancer progression, invasion, and metastasis in various cancer types. Axl overexpression has been observed in many cancers, and selective inhibitors of Axl, including R428, may be promising therapeutic agents for several human cancers, such as breast, lung, and pancreatic cancers. Here, we examined the cell growth inhibition mediated by R428 and auranofin individually as well as in combination in the human breast cancer cell lines MCF-7 and MDAMB- 231 to identify new advanced combination treatments for human breast cancer.

CYP1B1 prevents proteasome-mediated XIAP degradation by inducing PKCε activation and phosphorylation of XIAP.

Cytochrome P450 1B1 (CYP1B1) is a key enzyme that catalyzes the metabolism of 17β-estradiol (E2) into catechol estrogens, such as 2-hydroxyestradiol (2-OHE2) and 4-hydroxyestradiol (4-OHE2). CYP1B1 is related to tumor formation and is over-expressed in a variety of cancer cells. In particular, CYP1B1 is highly expressed in hormone-related cancers such as breast cancer, ovarian cancer, or prostate cancer compared to other cancers.

G0/G1 Switch 2 Induces Cell Survival and Metastasis through Integrin-Mediated Signal Transduction in Human Invasive Breast Cancer Cells.

Human breast cancer cell line, MDA-MB-231, is highly invasive and aggressive, compared to less invasive cell line, MCF-7. To explore the genes that might influence the malignancy of MDA-MB-231, DNA microarray analysis was performed. The results showed that G0/G1 switch 2 (G0S2) was one of the most highly expressed genes among the genes upregulated in MDA-MB-231.

Combination treatment with auranofin and nutlin-3a induces synergistic cytotoxicity in breast cancer cells.

Auranofin is a gold complex categorized as an anti-rheumatic agent. Recently, several investigators suggested that auranofin may act as a potent anti-cancer drug for breast tumors. Nutlin-3a is a cis-imidazoline analog which prevents interaction between mouse double minute 2 homolog (MDM2) and the tumor suppressor p53.

Human steroid sulfatase enhances aerobic glycolysis through induction of HIF1α and glycolytic enzymes.

Human steroid sulfatase (STS) has been linked with poor prognosis in steroid-associated tumors and represents an important clinical target in cancers, yet the mechanism of STS-induced carcinogenesis remains unclear. To correlate STS with cancer metabolism, we determined the effects of STS on aerobic glycolysis. STS overexpression increased cellular levels of lactic acid, the final product of aerobic glycolysis.

Discovery of Ezrin Expression as a Potential Biomarker for Chemically Induced Ocular Irritation Using Human Corneal Epithelium Cell Line and a Reconstructed Human Cornea-like Epithelium Model.

Numerous studies have attempted to develop a new in vitro eye irritation test (EIT). To obtain more reliable results from EIT, potential new biomarkers that reflect eye irritation by chemicals must be identified. We investigated candidate biomarkers for eye irritation, using a proteomics approach.

7,12-Dimethylbenz[α]anthracene increases cell proliferation and invasion through induction of Wnt/β-catenin signaling and EMT process.

7,12-Dimethylbenz[α]anthracene (DMBA) is a hazardous component present in polluted environments. DMBA has been used as an experimental tool for in vivo tumor formation owing to its carcinogenic effects, but the detailed molecular mechanism of DMBA has not been fully established. To comprehend the carcinogenic mechanism of DMBA, we explored its effects in the breast cancer cell lines, MCF-7 and MDA-MB-231, and the cervical cancer cell line, HeLa.

Cytochrome P450 1B1 promotes cancer cell survival via specificity protein 1 (Sp1)-mediated suppression of death receptor 4.

Cytochrome P450 1B1 (CYP1B1), a well-known oncogene, has garnered wide attention because of its tumor-specific expression pattern and actions as a carcinogenic factor. Although CYP1B1 might play a crucial role in carcinogenesis, the detailed molecular mechanisms underlying oncogenic involvement in cancer development remain unclear. The present study investigated the manner in which CYP1B1 promotes survival of various cancer cells.

Annexin A5 suppresses cyclooxygenase-2 expression by downregulating the protein kinase C-ζ-nuclear factor-κB signaling pathway in prostate cancer cells.

Annexin A5 (ANXA5) is a member of the annexin protein family. Previous studies have shown that ANXA5 is involved in anti-inflammation and cell death. However, the detailed mechanism of the role of ANXA5 in cancer cells is not well understood.

Human steroid sulfatase induces Wnt/β-catenin signaling and epithelial-mesenchymal transition by upregulating Twist1 and HIF-1α in human prostate and cervical cancer cells.

Steroid sulfatase (STS) catalyzes the hydrolysis of estrone sulfate and dehydroepiandrosterone sulfate (DHEAS) to their unconjugated biologically active forms. Although STS is considered a therapeutic target for estrogen-dependent diseases, the cellular functions of STS remain unclear. We found that STS induces Wnt/β-catenin s Delete ignaling in PC-3 and HeLa cells.

CYP1B1 Activates Wnt/β-Catenin Signaling through Suppression of Herc5-Mediated ISGylation for Protein Degradation on β-Catenin in HeLa Cells.

Cytochrome P450 1B1 (CYP1B1) acts as a hydroxylase for estrogen and activates potential carcinogens. Moreover, its expression in tumor tissues is much higher than that in normal tissues. Despite this association between CYP1B1 and cancer, the detailed molecular mechanism of CYP1B1 on cancer progression in HeLa cells remains unknown.

Synergistic induction of apoptosis by combination treatment with mesupron and auranofin in human breast cancer cells.

Urokinase-type plasminogen activator (uPA) has been validated as a predictive or prognostic biomarker protein, and mesupron is considered the first-in-class anticancer agent to inhibit uPA activity in human breast cancer. In the present study, we showed that the synergism between mesupron and auranofin, a thioredoxin reductase inhibitor, for inducing of apoptosis in MCF-7 human breast cancer cells. Our results demonstrated that mesupron and auranofin significantly lead to inhibition of the cancer cells proliferation; cell cycle arrest at the G1/S phase of the cell cycle, and apoptosis as indicated by caspase 3 activation, poly(ADP-ribose) polymerase cleavage, and annexin V staining.

Auranofin Suppresses Plasminogen Activator Inhibitor-2 Expression through Annexin A5 Induction in Human Prostate Cancer Cells.

Auranofin has been developed as antirheumatic drugs, which is currently under clinical development for the treatment of chronic lymphocytic leukemia. Previous report showed that auranofin induced apoptosis by enhancement of annexin A5 expression in PC-3 cells. To understand the role of annexin A5 in auranofin-mediated apoptosis, we performed microarray data analysis to study annexin A5-controlled gene expression in annexin A5 knockdown PC-3 cells.