IL-13Rα2 mediates PNR-induced migration and metastasis in ERα-negative breast cancer

Zhao, Zibo; Wang, Lu; Xu, Wei

doi:10.1038/onc.2014.53

Cited by 35 publications

(29 citation statements)

References 60 publications

(91 reference statements)

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“…Retroviruses and lentiviruses were packaged as previously described (Zhao et al, 2014). To generate stable cell lines, cells were selected for a week with 800 μg/ml G418 (RPI, Mount Prospect, IL) for Flag-ERβ overexpression or with 2 μg/ml puromycin (RPI) for CHIP E3 ligase and ERβ knockdown.…”

Section: Methodsmentioning

confidence: 99%

Reciprocal Regulation of ERα and ERβ Stability and Activity by Diptoindonesin G

Zhao

Wang

James

et al. 2015

Chemistry & Biology

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Summary ERβ is regarded as a “tumor suppressor” in breast cancer due to its anti-proliferative effects. However, unlike ERα, ERβ has not been developed as a therapeutic target in breast cancer due to loss of ERβ in aggressive cancers. In a small molecule library screen for ERβ stabilizers, we identified Diptoindonesin G (Dip G) which significantly increases ERβ protein stability, while decreasing ERα protein levesl. Dip G enhances the transcription and anti-proliferative activities of ERβ, while attenuating the transcription and proliferative effects of ERα. Further investigation revealed that instead of targeting ER, Dip G targets the CHIP E3 ubiquitin ligase shared by ERα and ERβ. Thus, Dip G is a dual functional moiety that reciprocally controls ERα and ERβ protein stability and activities via an indirect mechanism. The ERβ stabilization effects of Dip G may enable the development of ERβ-targeted therapies for human breast cancers.

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Section: Methodsmentioning

confidence: 99%

Reciprocal Regulation of ERα and ERβ Stability and Activity by Diptoindonesin G

Zhao

Wang

James

et al. 2015

Chemistry & Biology

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“…By converse, over-expression of the nuclear receptor stimulates the formation of mammospheres, the growth and the invasive behavior of ER − MDA-MB231 cells [121]. NR2E3 is an ERα transcriptional activator [122] and it may contribute to hormone-dependent growth of ER + /tumors, although high NR2E3 levels are associated with favorable responses to tamoxifen. NR2E3 oncogenic action may extend to ER − /tumors, inducing MDA-MB-231 cell migration in-vitro and metastatic spread in-vivo [122].…”

Section: Orphan Receptorsmentioning

confidence: 99%

“…NR2E3 is an ERα transcriptional activator [122] and it may contribute to hormone-dependent growth of ER + /tumors, although high NR2E3 levels are associated with favorable responses to tamoxifen. NR2E3 oncogenic action may extend to ER − /tumors, inducing MDA-MB-231 cell migration in-vitro and metastatic spread in-vivo [122]. …”

Section: Orphan Receptorsmentioning

confidence: 99%

Lipid-sensors, enigmatic-orphan and orphan nuclear receptors as therapeutic targets in breast-cancer

et al. 2016

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Breast-cancer is heterogeneous and consists of various groups with different biological characteristics. Innovative pharmacological approaches accounting for this heterogeneity are needed. The forty eight human Nuclear-Hormone-Receptors are ligand-dependent transcription-factors and are classified into Endocrine-Receptors, Adopted-Orphan-Receptors (Lipid-sensors and Enigmatic-Orphans) and Orphan-receptors. Nuclear-Receptors represent ideal targets for the design/synthesis of pharmacological ligands. We provide an overview of the literature available on the expression and potential role played by Lipid-sensors, Enigmatic-Orphans and Orphan-Receptors in breast-cancer. The data are complemented by an analysis of the expression levels of each selected Nuclear-Receptor in the PAM50 breast-cancer groups, following re-elaboration of the data publicly available. The major aim is to support the idea that some of the Nuclear-Receptors represent largely unexploited therapeutic-targets in breast-cancer treatment/chemo-prevention. On the basis of our analysis, we conclude that the Lipid-Sensors, NR1C3, NR1H2 and NR1H3 are likely to be onco-suppressors in breast-cancer. The Enigmatic-Orphans, NR1F1 NR2A1 and NR3B3 as well as the Orphan-Receptors, NR0B1, NR0B2, NR1D1, NR2F1, NR2F2 and NR4A3 exert a similar action. These Nuclear-Receptors represent candidates for the development of therapeutic strategies aimed at increasing their expression or activating them in tumor cells. The group of Nuclear-Receptors endowed with potential oncogenic properties consists of the Lipid-Sensors, NR1C2 and NR1I2, the Enigmatic-Orphans, NR1F3, NR3B1 and NR5A2, as well as the Orphan-Receptors, NR2E1, NR2E3 and NR6A1. These oncogenic Nuclear-Receptors should be targeted with selective antagonists, reverse-agonists or agents/strategies capable of reducing their expression in breast-cancer cells.

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“…However, an increasing number of studies have shown that IL‐13Rα2 may have some signaling functions. There are recent evidences that found IL‐13Rα2 to be highly expressed in various solid tumors to mediate cancer metastasis by inducing downstream pathways ERK/AP‐1, PI3K/AKT, or ERK/PNR . In human airways, S. Fichtner‐Feigl found that IL‐13Rα2 is involved in IL‐13 signaling through the transcription factor AP‐1 to induce the activation of TGF‐β in lung fibrosis .…”

Section: Introductionmentioning

confidence: 99%