Regulation of cancer stem cell properties, angiogenesis, and vasculogenic mimicry by miR-450a-5p/SOX2 axis in colorectal cancer

Chen, Jiaxuan; Chen, Shengyuan; Zhuo, Linghao; Zhu, Yu; Zheng, Haoxuan

doi:10.1038/s41419-020-2361-z

Cited by 44 publications

(41 citation statements)

References 36 publications

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“…Cell vasculogenic mimicry was calculated via three‐dimensional assay as reported previously 28 . Different concentrations of Sal‐A (0–50 µmol/L) were treated with NSCLC cells for 24 hours.…”

Section: Methodsmentioning

confidence: 99%

Salvianolic acid A blocks vasculogenic mimicry formation in human non‐small cell lung cancer via PI3K/Akt/mTOR signalling

Jin

Chen

Huang

et al. 2021

Clin Exp Pharma Physio

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Vasculogenic mimicry (VM) is associated with aggressive cancer cells. Salvianolic acid A (Sal‐A), an antioxidant and anti‐inflammatory agent, has bioactive properties from Salvia miltiorrhiza Bunge. Current investigation aspired to explore the activity of Sal‐A in the VM formation of non‐small cell lung cancer (NSCLC) and the mechanism underling this function. The CCK8, the scratch and boyden chemotaxis assay were presented to describe NSCLC cells viability, migration and invasion capabilities, respectively. The protein expression was verified by western blotting. In this report, Sal‐A caused a reduction in viability, metastasis and capillaries structure formation of NSCLC cells. Additionally, Sal‐A markedly prevented the key VM related proteins, containing EphA2, VE‐cadherin and MMP2. Besides, Sal‐A significantly diminished p‐PI3K, p‐Akt and p‐mTOR level in NSCLC cells. More importantly, SC79 pretreatment reversed Sal‐A inhibits NSCLC cells viability, metastasis and VM formation. These data exhibit that Sal‐A could block VM network formation in NSCLC cells through modulating the PI3K/Akt/mTOR signalling pathway.

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Section: Methodsmentioning

confidence: 99%

Salvianolic acid A blocks vasculogenic mimicry formation in human non‐small cell lung cancer via PI3K/Akt/mTOR signalling

Jin

Chen

Huang

et al. 2021

Clin Exp Pharma Physio

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“…Sex-determining region Y-box2 (SOX2), a master regulator of embryonic and induced pluripotent stem cells (iPSCs), drives cancer stemness, fuels tumor initiation, and contributes to tumor aggressiveness 4 . In our recent study, we found that SOX2 promotes chemoresistance, confers CSCs properties, and promotes epithelial–mesenchymal transition (EMT) in colorectal cancer (CRC) 5 . However, the underlying mechanism of this phenomenon is not well-characterized.…”

Section: Introductionmentioning

confidence: 99%

SOX2 promotes chemoresistance, cancer stem cells properties, and epithelial–mesenchymal transition by β-catenin and Beclin1/autophagy signaling in colorectal cancer

et al. 2021

Self Cite

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Sex-determining region Y-box2 (SOX2), a master regulator of embryonic and induced pluripotent stem cells, drives cancer stem cells (CSCs) properties, fuels tumor initiation, and contributes to tumor aggressiveness. Our previous study has demonstrated the oncogenic role of SOX2 in colorectal cancer (CRC). In this study, we sought to elucidate the underlying mechanisms. Cell function experiments were performed to detect chemoresistance, proliferation, stemness, migration, and invasion in vitro. Chromatin immunoprecipitation, co-immunoprecipitation, luciferase reporter assay, and immunofluorescence were performed to explore the regulation of ABCC2, β-catenin, and Beclin1 by SOX2. The carcinogenic role of SOX2-β-catenin/Beclin1-ABCC2 axis in vivo was analyzed by CRC tissues and xenograft models. Here, we reported that SOX2 sustained chemoresistance by transcriptional activation of ABCC2 expression. Suppressing either β-catenin or autophagy signaling curbed SOX2-driven chemoresistance, stemness, and epithelial–mesenchymal transition (EMT). Mechanistically, SOX2 combined with β-catenin and increased its nuclear expression and transcriptional activity. Transcriptional activation of Beclin1 expression by SOX2 consequently activating autophagy and inducing malignant phenotype. Furthermore, overexpression of β-catenin or Beclin1 facilitated ABCC2 expression. The clinical analyses showed that high expression of ABCC2 and Beclin1 were positively correlated with SOX2 and were associated with poor prognosis in CRC patients. Finally, xenograft models revealed that inhibition of SOX2 expression and autophagy restrained tumor growth and chemoresistance in vivo. Conclusively, we demonstrated a novel mechanism by which the SOX2-β-catenin/Beclin1/autophagy signaling axis regulates chemoresistance, stemness, and EMT in CRC. Our findings provide novel insights into CRC carcinogenesis and may help develop potential therapeutic candidates for CRC.

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“…2). Among JICD1-upregulated DEGs, SOX2 plays a pivotal role in the maintenance of embryonic and neural stem cells and is associated with cancer progression in numerous solid tumors 29,30,31 . To confirm the oncogenic function of SOX2, we established SOX2-overexpressing cells (Supplementary Fig.…”

Section: Jicd1 Exerts Oncogenic Functions By Regulating Sox2 Expressionmentioning

confidence: 99%

JAG1 intracellular domain acts as a transcriptional cofactor that forms an oncogenic transcriptional complex with DDX17/SMAD3/TGIF2

Kim

et al. 2021

Preprint

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Jagged1 (JAG1) is a Notch ligand that contact-dependently activates Notch receptors and regulates cancer progression. The JAG1 intracellular domain (JICD1) is generated from JAG1, such as the formation of NOTCH1 intracellular domain (NICD1), however, the role of JICD1 in tumorigenicity has not been comprehensively elucidated. Herein, we revealed that JICD1 induced astrocytes to acquire several cancer stem cell properties, including tumor formation, invasiveness, stemness, and resistance to chemotherapy and radiotherapy. The transcriptome, ChIP-sequencing, and proteomic analyses revealed that JICD1 increased SOX2 expression by forming a transcriptional complex with DDX17, SMAD3, and TGIF2. Furthermore, JICD1-driven tumorigenicity was directly regulated by SOX2. Therefore, our results demonstrated that, like NICD1, JICD1 acts as a transcriptional cofactor in the formation of the DDX17/SMAD3/TGIF2 transcriptional complex, leading to oncogenic transformation.

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Regulation of cancer stem cell properties, angiogenesis, and vasculogenic mimicry by miR-450a-5p/SOX2 axis in colorectal cancer

Cited by 44 publications

References 36 publications

Salvianolic acid A blocks vasculogenic mimicry formation in human non‐small cell lung cancer via PI3K/Akt/mTOR signalling

Salvianolic acid A blocks vasculogenic mimicry formation in human non‐small cell lung cancer via PI3K/Akt/mTOR signalling

SOX2 promotes chemoresistance, cancer stem cells properties, and epithelial–mesenchymal transition by β-catenin and Beclin1/autophagy signaling in colorectal cancer

JAG1 intracellular domain acts as a transcriptional cofactor that forms an oncogenic transcriptional complex with DDX17/SMAD3/TGIF2

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