A novel function of R-spondin1 in regulating estrogen receptor expression independent of Wnt/β-catenin signaling

Geng, Ajun; Wu, Ting; Cai, Cheguo; Song, Wenqian; Wang, Jiqiu; Yu, Qing; Zeng, Yi Arial

doi:10.7554/elife.56434

Cited by 24 publications

(22 citation statements)

References 51 publications

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“…Notably, in the control group ESR1 was mainly located in the nucleus, while in the baicalin-treated group ESR1 localized to the cytoplasm ( Figure 4G ). To investigate whether baicalin regulates the transcription of Esr 1, we utilized a luciferase reporter driven by the proximal promoter of mouse Esr1 ( Geng et al, 2020 ). We found that luciferase activity was down-regulated by baicalin in a dose-dependent manner ( Figure 4H ).…”

Section: Resultsmentioning

confidence: 99%

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Baicalin Promotes Mammary Gland Development via Steroid-Like Activities

Chen

Wei

et al. 2021

Front. Cell Dev. Biol.

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Baicalin, the main flavonoid component extracted from Scutellaria roots, has a variety of biological activities and is therefore used in the treatment of many kinds of diseases. However, whether baicalin affects the normal development of tissues and organs is still unclear. Here, using a mouse mammary gland model, we investigated the effects of baicalin on the expansion of mammary stem cells (MaSCs) and mammary development, as well as breast cancer progression. Interestingly, we found that baicalin administration significantly accelerates duct elongation at puberty, and promotes alveolar development and facilitates milk secretion during pregnancy. Furthermore, self-renewal of MaSCs was significantly promoted in the presence of baicalin. Moreover, in a tumor xenograft model, baicalin promoted tumor growth of the MDA-MB-231 cell line, but suppressed tumor growth of the ZR-751 cell line. Mechanistically, baicalin can induce expression of the protein C receptor, while inhibiting the expression of the estrogen receptor. Transcriptome analysis revealed that baicalin is involved in signaling pathways related to mammary gland development, immune response, and cell cycle control. Taken together, our results from comprehensive investigation of the biological activity of baicalin provide a theoretical basis for its rational clinical application.

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Section: Resultsmentioning

confidence: 99%

“…The Procr and Esr1 promoters were separately cloned into the pGL4.17 vector to generate the luciferase reporters ( Geng et al, 2020 ). 293T cells were plated into 24-well tissue culture dishes.…”

Section: Methodsmentioning

confidence: 99%

Baicalin Promotes Mammary Gland Development via Steroid-Like Activities

Chen

Wei

et al. 2021

Front. Cell Dev. Biol.

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“…6 The activation of β-catenin is accompanied by the loss of mito- could be activated by Wnt-triggered inhibition on its degradation 35 and also could be stimulated by GPCR-induced signal wave. 15,36,37 Interestingly, we have found several GPCRs such CXCR4 and CB2 induce the kidney injury depending on β-catenin activation. 15,36 CB2 was recently found to be primarily upregulated in the proximal and distal tubules in renal fibrosis model and promoted kidney fibrosis by orchestrating β-catenin signalling, as reported by our recent work.…”

Section: Discussionmentioning

confidence: 96%

“…The activation of β‐catenin is accompanied by the loss of mitochondria mass and overproduced ROS, suggesting the highly intimate correlation of β‐catenin with mitochondrial dysfunction. β‐catenin could be activated by Wnt‐triggered inhibition on its degradation 35 and also could be stimulated by GPCR‐induced signal wave 15,36,37 …”

Section: Discussionmentioning

confidence: 99%

Cannabinoid receptor 2 plays a central role in renal tubular mitochondrial dysfunction and kidney ageing

Zhou

Ling

Meng

et al. 2021

J Cellular Molecular Medi

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Kidney is one of the most important organs in maintaining the normal life activities. With the high abundance of mitochondria, renal tubular cell plays the vital role in functioning in the reabsorption and secretion of kidney. Reports have shown that mitochondrial dysfunction is of great importance to renal tubular cell senescence and subsequent kidney ageing. However, the underlying mechanisms are not elucidated. Cannabinoid receptor 2 is one of the two receptors responsible for the activation of endocannabinoid system. CB2 is primarily upregulated in renal tubular cells in chronic kidney diseases and mediates fibrogenesis. However, the role of CB2 in tubular mitochondrial dysfunction and kidney ageing has not been clarified. In this study, we found that CB2 was upregulated in kidneys in 24‐month‐old mice and d‐galactose (d‐gal)‐induced accelerated ageing mice, accompanied by the decrease in mitochondrial mass. Furthermore, gene deletion of CB2 in d‐gal‐treated mice could greatly inhibit the activation of β‐catenin signalling and restore the mitochondrial integrity and Adenosine triphosphate (ATP) production. In CB2 knockout mice, renal tubular cell senescence and kidney fibrosis were also significantly inhibited. CB2 overexpression or activation by the agonist AM1241 could sufficiently induce the decrease in PGC‐1α and a variety of mitochondria‐related proteins and trigger cellular senescence in cultured human renal proximal tubular cells. CB2‐activated mitochondrial dysfunction and cellular senescence could be blocked by ICG‐001, a blocker for β‐catenin signalling. These results show CB2 plays a central role in renal tubular mitochondrial dysfunction and kidney ageing. The intrinsic mechanism may be related to its activation in β‐catenin signalling.

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“…A recent work reports that R-spondin 1 (RSPO1), a niche factor secreted by the ERα-negative luminal cells, regulates ERα expression through paracrine mechanisms [197]. RSPO1 is known to bind LGR receptors and synergize with WNT4 to enhance Wnt/βcat signaling in mammary basal cells.…”

Section: Erα + Unipotent Stem Cellsmentioning

confidence: 99%

Estrogen receptor-α signaling in post-natal mammary development and breast cancers

Rusidzé

Adlanmérini

Chantalat

et al. 2021

Cell. Mol. Life Sci.

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Abstract17β-estradiol controls post-natal mammary gland development and exerts its effects through Estrogen Receptor ERα, a member of the nuclear receptor family. ERα is also critical for breast cancer progression and remains a central therapeutic target for hormone-dependent breast cancers. In this review, we summarize the current understanding of the complex ERα signaling pathways that involve either classical nuclear “genomic” or membrane “non-genomic” actions and regulate in concert with other hormones the different stages of mammary development. We describe the cellular and molecular features of the luminal cell lineage expressing ERα and provide an overview of the transgenic mouse models impacting ERα signaling, highlighting the pivotal role of ERα in mammary gland morphogenesis and function and its implication in the tumorigenic processes. Finally, we describe the main features of the ERα-positive luminal breast cancers and their modeling in mice.

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A novel function of R-spondin1 in regulating estrogen receptor expression independent of Wnt/β-catenin signaling

Cited by 24 publications

References 51 publications

Baicalin Promotes Mammary Gland Development via Steroid-Like Activities

Baicalin Promotes Mammary Gland Development via Steroid-Like Activities

Cannabinoid receptor 2 plays a central role in renal tubular mitochondrial dysfunction and kidney ageing

Estrogen receptor-α signaling in post-natal mammary development and breast cancers

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