Msi1 promotes tumor progression by epithelial-to-mesenchymal transition in cervical cancer

Gong, Pijun; Wang, Yidong; Gao, Yue; Gao, Mei; Liu, Lixia; Qü, Ping; Jin, Xin-Xing; Gao, Qing

doi:10.1016/j.humpath.2016.12.026

Cited by 19 publications

(11 citation statements)

References 37 publications

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“…Interestingly, we noted upregulation of EMT-promoting genes with 2APB and TGF-β addition, including Osm [ 26 , 27 ], Msi1 [ 28 ] and 2 610018G03Rik ( Mst4 ) [ 29 ]. On the other hand, one of the top ten genes that is upregulated with 2APB during TGF-β induced EMT was Reln , which was previously shown to prevent TGF-β induced migration [ 30 ].…”

Section: Resultsmentioning

confidence: 99%

The calcium channel proteins ORAI3 and STIM1 mediate TGF-β inducedSnai1expression

et al. 2018

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Calcium influx into cells via plasma membrane protein channels is tightly regulated to maintain cellular homeostasis. Calcium channel proteins in the plasma membrane and endoplasmic reticulum have been linked to cancer, specifically during the epithelial-mesenchymal transition (EMT), a cell state transition process implicated in both cancer cell migration and drug resistance. The transcription factor SNAI1 (SNAIL) is upregulated during EMT and is responsible for gene expression changes associated with EMT, but the calcium channels required for Snai1 expression remain unknown. In this study, we show that blocking store-operated calcium entry (SOCE) with 2-aminoethoxydiphenylborane (2APB) reduces cell migration but, paradoxically, increases the level of TGF-β dependent Snai1 gene activation. We determined that this increased Snai1 transcription involves signaling through the AKT pathway and subsequent binding of NF-κB (p65) at the Snai1 promoter in response to TGF-β. We also demonstrated that the calcium channel protein ORAI3 and the stromal interaction molecule 1 (STIM1) are required for TGF-β dependent Snai1 transcription. These results suggest that calcium channels differentially regulate cell migration and Snai1 transcription, indicating that each of these steps could be targeted to ensure complete blockade of cancer progression.

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Section: Resultsmentioning

confidence: 99%

The calcium channel proteins ORAI3 and STIM1 mediate TGF-β inducedSnai1expression

et al. 2018

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“…Although the roles of MSI1 in different cancers extensively correlated with proliferation of cancer cells, its role in cancer cell migration and invasion proffers a much broader role. A recent study has shown a positive correlation between MSI1 and epithelial-mesenchymal markers, vimentin, and snail in tissues of cervical cancer [41]. On the other hand, MSI1 knockdown decreases proliferation of cancer stem cells and induces apoptosis in solid tumors.…”

Section: Association Of Msi1 Expression and Cancersmentioning

confidence: 98%

Intracellular functions of RNA-binding protein, Musashi1, in stem and cancer cells

et al. 2020

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RNA-binding protein, musashi1 (MSI1), is a main protein in asymmetric cell division of the sensory organ precursor cells, whereas its expression is reported to be upregulated in cancers. This protein is a critical element in proliferation of stem and cancer stem cells, which acts through Wnt and Notch signaling pathways. Moreover, MSI1 modulates malignancy and chemoresistance of lung cancer cells via activating the Akt signaling. Due to the main role of MSI1 in metastasis and cancer development, MSI1 would be an appropriate candidate for cancer therapy. Downregulation of MSI1 inhibits proliferation of cancer stem cells and reduces the growth of solid tumors in several cancers. On the other hand, MSI1 expression is regulated by microRNAs in such a way that several different tumor suppressor miRNAs negatively regulate oncogenic MSI1 and inhibit migration and tumor metastasis. The aim of this review is summarizing the role of MSI1 in stem cell proliferation and cancer promotion.

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“…Msi1 modulates cell growth and cell cycle in hepatoma by activation of Wnt pathway via inhibition of APC and DKK1 [41]. In cervical cancer, silencing of Msi1 inhibited cell migration, invasion as well as epithelial-to-mesenchymal transition (EMT) through activation of the Wnt signaling pathway [42]. In breast and lung cancers, Notch and Wnt pathways are also Msi1's preferential routes of action [22,43].…”

Section: Musashi1 As Oncogenic Factor In Multiple Tumor Typesmentioning

confidence: 99%

Luteolin inhibits Musashi1 binding to RNA and disrupts cancer phenotypes in glioblastoma cells

Li²,

Ivanov

et al. 2018

RNA Biology

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RNA binding proteins have emerged as critical oncogenic factors and potential targets in cancer therapy. In this study, we evaluated Musashi1 (Msi1) targeting as a strategy to treat glioblastoma (GBM); the most aggressive brain tumor type. Msi1 expression levels are often high in GBMs and other tumor types and correlate with poor clinical outcome. Moreover, Msi1 has been implicated in chemo-and radio-resistance. Msi1 modulates a range of cancer relevant processes and pathways and regulates the expression of stem cell markers and oncogenic factors via mRNA translation/stability. To identify Msi1 inhibitors capable of blocking its RNA binding function, we performed a~25,000 compound fluorescence polarization screen. NMR and LSPR were used to confirm direct interaction between Msi1 and luteolin, the leading compound. Luteolin displayed strong interaction with Msi1 RNA binding domain 1 (RBD1). As a likely consequence of this interaction, we observed via western and luciferase assays that luteolin treatment diminished Msi1 positive impact on the expression of pro-oncogenic target genes. We tested the effect of luteolin treatment on GBM cells and showed that it reduced proliferation, cell viability, colony formation, migration and invasion of U251 and U343 GBM cells. Luteolin also decreased the proliferation of patient-derived glioma initiating cells (GICs) and tumor-organoids but did not affect normal astrocytes. Finally, we demonstrated the value of combined treatments with luteolin and olaparib (PARP inhibitor) or ionizing radiation (IR). Our results show that luteolin functions as an inhibitor of Msi1 and demonstrates its potential use in GBM therapy.

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Msi1 promotes tumor progression by epithelial-to-mesenchymal transition in cervical cancer

Cited by 19 publications

References 37 publications

The calcium channel proteins ORAI3 and STIM1 mediate TGF-β inducedSnai1expression

The calcium channel proteins ORAI3 and STIM1 mediate TGF-β inducedSnai1expression

Intracellular functions of RNA-binding protein, Musashi1, in stem and cancer cells

Luteolin inhibits Musashi1 binding to RNA and disrupts cancer phenotypes in glioblastoma cells

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