Induction of steroid sulfatase expression by tumor necrosis factor-α through phosphatidylinositol 3-kinase/Akt signaling pathway in PC-3 human prostate cancer cells

Suh, Bo Young; Jung, Jin Joo; Park, Nahee; Seong, Cheul Hun; Im, Hee Jung; Kwon, Yeo‐Jung; Kim, Donghak; Chun, Young Jin

doi:10.3858/emm.2011.43.11.073

Cited by 15 publications

(8 citation statements)

References 30 publications

(34 reference statements)

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“…In addition to the potential for estrogens to regulate STS activity, the proinflammatory cytokines IL-6 and TNFα alter STS enzyme kinetics. MCF7 cells increase STS activity in response to IL-6 and TNFα without alteration in STS mRNA levels ( 57 , 58 ), a trait also noted in other cancer cell lines ( 59 ). This suggests that post-translational modifications, possibly via STS glycosylation, are involved in regulating STS activity ( 17 , 60 , 61 ).…”

Section: Steroid Sulfatasesmentioning

confidence: 70%

“…Knockdown of SULT1B1 in LNCaP cells increases DHEA-induced proliferation ( 326 ), implying that the STS/SULT1B1 ratio in the prostate regulates DHEAS/DHEA-induced proliferation. This ratio is likely to be influenced by local inflammatory conditions, as shown by Suh et al ( 59 ) who assessed whether TNFα can induce STS expression; LNCap and PC-3 cells up-regulated STS expression in a TNFα concentration and time-dependent manner. They further demonstrated that at least part of this effect was via the phosphatidylinositol 3 (PI3)-kinase/Akt pathway because PI3-kinase inhibitors and AKT inhibitors suppressed STS mRNA up-regulation induced by TNFα.…”

Section: Dysregulation Of Steroid Sulfation and Desulfationmentioning

confidence: 95%

“…Several sulfate transporters are responsible for cellular sulfate uptake (reviewed in Refs. 59 and 62 ), followed by the two-step enzymatic sulfate activation by bifunctional PAPS synthases. PAPS is then either used directly by cytoplasmic and nuclear sulfotransferases or shuttled to the Golgi apparatus to serve a multitude of Golgi-residing carbohydrate and protein sulfotransferases.…”

Section: Steroid Sulfotransferases and Paps Synthasesmentioning

confidence: 99%

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The Regulation of Steroid Action by Sulfation and Desulfation

et al. 2015

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Steroid sulfation and desulfation are fundamental pathways vital for a functional vertebrate endocrine system. After biosynthesis, hydrophobic steroids are sulfated to expedite circulatory transit. Target cells express transmembrane organic anion-transporting polypeptides that facilitate cellular uptake of sulfated steroids. Once intracellular, sulfatases hydrolyze these steroid sulfate esters to their unconjugated, and usually active, forms. Because most steroids can be sulfated, including cholesterol, pregnenolone, dehydroepiandrosterone, and estrone, understanding the function, tissue distribution, and regulation of sulfation and desulfation processes provides significant insights into normal endocrine function. Not surprisingly, dysregulation of these pathways is associated with numerous pathologies, including steroid-dependent cancers, polycystic ovary syndrome, and X-linked ichthyosis. Here we provide a comprehensive examination of our current knowledge of endocrine-related sulfation and desulfation pathways. We describe the interplay between sulfatases and sulfotransferases, showing how their expression and regulation influences steroid action. Furthermore, we address the role that organic anion-transporting polypeptides play in regulating intracellular steroid concentrations and how their expression patterns influence many pathologies, especially cancer. Finally, the recent advances in pharmacologically targeting steroidogenic pathways will be examined.

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Section: Steroid Sulfatasesmentioning

confidence: 70%

Section: Dysregulation Of Steroid Sulfation and Desulfationmentioning

confidence: 95%

Section: Steroid Sulfotransferases and Paps Synthasesmentioning

confidence: 99%

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The Regulation of Steroid Action by Sulfation and Desulfation

et al. 2015

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“…Because cytosolic β-catenin accumulation induces its translocation into the nucleus, where it interacts with various transcription factors of the TCF family such as TCF4, we determined whether STS increases β-catenin/TCF4 transcriptional activity [ 17 , 19 , 38 – 40 ]. STS expression induced β-catenin accumulation in the nucleus, and the level of cyclin D1, a downstream target of β-catenin, was also strongly increased (Figure 2A ).…”

Section: Resultsmentioning

confidence: 99%

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

Shin

Kwon

et al. 2017

Oncotarget

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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. STS increases levels of β-catenin, phospho-β-catenin, and phospho-GSK3β. Enhanced translocation of β-catenin to the nucleus by STS might activate transcription of target genes such as cyclin D1, c-myc, and MMP-7. STS knockdown by siRNA resulted in downregulation of Wnt/β-catenin signaling. β-Catenin/TCF-mediated transcription was also enhanced by STS. STS induced an epithelial-mesenchymal transition (EMT) as it reduced the levels of E-cadherin, whereas levels of mesenchymal markers such as N-cadherin and vimentin were enhanced. We found that STS induced Twist1 expression through HIFα activation as HIF-1α knockdown significantly blocks the ability of STS to induce Twist1 transcription. Furthermore, DHEA, but not DHEAS is capable of inducing Twist1. Treatment with a STS inhibitor prevented STS-mediated Wnt/β-catenin signaling and Twist1 expression. Interestingly, cancer cell migration, invasion, and MMPs expression induced by STS were also inhibited by a STS inhibitor. Taken together, these results suggest that STS induces Wnt/β-catenin signaling and EMT by upregulating Twist1 and HIF-1α. The ability of STS to induce the Wnt/β-catenin signaling and EMT has profound implications on estrogen-mediated carcinogenesis in human cancer cells.

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“…Suh et al recently reported that TNFα induces STS gene expression through a PI 3-kinase/ Akt signaling pathway in PC-3 human prostate cancer cells. 27) They also described the possible involvement of NF-κB in this induction. However, we found that treatment of SVHK cells with TNFα did not induce any significant increase in STS gene expression (Hattori et al, unpublished observation).…”

Section: Discussionmentioning

confidence: 99%

Interferon Gamma Induces Steroid Sulfatase Expression in Human Keratinocytes

Hattori

Yamaguchi

Umezawa

et al. 2012

Biological & Pharmaceutical Bulletin

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Key words steroid sulfatase; keratinocyte; interferon gamma; nuclear factor-kappa B; dexamethasone Steroid sulfatase (STS) is a microsomal enzyme that catalyzes the hydrolysis of sulfated 3-hydroxysteroids to the corresponding free active 3-hydroxysteroids.1) This enzyme is widely distributed throughout the body, and its actions are implicated in both physiological processes and pathological conditions. In many peripheral organs such as skin STS play a key role in the production of dehydroepiandrosterone (DHEA) from DHEA sulfate, which is abundant in the circulation. DHEA is then used as a major precursor for the synthesis of potent androgens in the skin.2) Early studies in vitro and in vivo have shown that the human STS activity appears in specific skin types, such as in foreskin and infantile abdominal skin, after birth.3) It also has been shown that STS plays an important functional role in the skin as this enzyme is deficient in X-linked ichthyosis (X-LI). 4,5) It has been further demonstrated that both the expression of STS mRNA and its enzymatic activity are increased in malignant breast and endometrial tissues compared with nonmalignant tissues and that this increased STS affects active estrogen levels within cells by hydrolysis of inactive estrogen sulfates. 6) We recently reported that estradiol sulfate, whose formation is catalyzed by estrogen sulfotransferase, is a major metabolite of estradiol in human epidermal keratinocytes. 7) Since estrogens have a significant effect on skin differentiation and development, 8,9) the activity of STS, as well as of estrogen sulfotransferase in the skin must be properly regulated to maintain cutaneous homeostasis. However, little is known about the regulation of STS gene expression or activity in skin.It has been reported previously that interleukin-6 (IL-6) and tumor necrosis factor alpha (TNFα) act synergistically to increase STS activity in breast cancer cells, 10,11) and that this effect on STS activity is regulated by posttranslational modification of a cysteine residue in the catalytically active site of this enzyme to formyl glycine. In contrast, the inflammatory cytokine IL-1β decreases STS activity and the expression of STS mRNA in human endometrial stromal cells.12) In psoriatic plaques in skin, there is a predominance of T helper 1 cytokines, most notably interferon gamma (IFNγ).13) IFNγ is a cytokine that is produced by activated T cells and natural killer cells, and induces a variety of effects including anti-viral responses, cell growth and differentiation. 14) In the skin, IFNγ is known to play a pivotal role in the development of inflammatory and immune responses. [15][16][17] However, no information is available concerning the effect of IFNγ on STS expression. IFNγ has been reported to stimulate involucrin gene expression via STAT1 signaling in cells of the SVHK cell line that was established from SV40-transformed human keratinocytes. 18,19) To determine the effect of IFNγ on STS expression in the human epidermis, we investigated the effects of IFNγ...

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Induction of steroid sulfatase expression by tumor necrosis factor-α through phosphatidylinositol 3-kinase/Akt signaling pathway in PC-3 human prostate cancer cells

Cited by 15 publications

References 30 publications

The Regulation of Steroid Action by Sulfation and Desulfation

The Regulation of Steroid Action by Sulfation and Desulfation

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

Interferon Gamma Induces Steroid Sulfatase Expression in Human Keratinocytes

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