FZD2 Promotes TGF-β-induced Epithelial-to-Mesenchymal Transition in Breast Cancer via Activating Notch Signaling Pathway

Abstract Background: Breast cancer (BC) is one of the commonest female cancers, which is characterized with high incidence. Although treatments have been improved, the prognosis of BC patients in advanced stages remains unsatisfactory. Thus, exploration of the molecular mechanisms underneath BC progression is necessary to find novel therapeutic methods. Frizzled class receptor (FZD2) belongs to Frizzled family, which has been proven to promote cell growth and invasion in various human cancers. The purpose of our current study was to detect the functions of FZD2 in BC and explore its underlying molecular mechanism.Methods: The level of FZD2 was measured in BC tissues by quantitative real-time polymerase chain reaction (qRT-PCR), western blot, immunohistochemistry (IHC), respectively. Cell Counting Kit-8 (CCK-8), colony formation assay, transwell assays, wound healing assay and flow cytometry analyses were separately conducted to detect cell viability, invasion, migration, apoptosis and cell cycle distribution. The levels of Epithelial-mesenchymal transition (EMT) biomarkers were examined by using Immunofluorescence assay. Xenograft tumorigenicity assay was performed to assess the effect of FZD2 on tumor growth in vivo.Results: FZD2 mRNA and protein expression was abundant in BC tissues. Moreover, high level of FZD2 had significant correlation with poor prognosis in BC patients. In vitro functional assays revealed that silencing of FZD2 had suppressive effects on BC cell growth, migration and invasion. Animal study further demonstrated that FZD2 silencing inhibited BC cell growth in vivo. In addition, FZD2 induced EMT process in BC cells in a transforming growth factor (TGF)-β1-dependent manner. Mechanistically, knockdown of FZD2 led to the inactivation of Notch signaling pathway.Conclusion: FZD2 facilitates BC progression and promotes TGF-β1-inudced EMT process through activating Notch signaling pathway.

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FZD2 Promotes TGF-β-Induced Epithelial-to-Mesenchymal Transition in Breast Cancer via Activating Notch Signaling Pathway

10.21203/rs.3.rs-63207/v1 ◽

2020 ◽

Author(s):

Dilihumaer Tuluhong ◽

Tao Chen ◽

Jingjie Wang ◽

Huijuan Zeng ◽

Hanjun Li ◽

...

Keyword(s):

Breast Cancer ◽

Cell Growth ◽

Notch Signaling ◽

Signaling Pathway ◽

Notch Signaling Pathway ◽

Cell Counting ◽

Dependent Manner ◽

Mesenchymal Transition ◽

Tgf Β1

Abstract Background Breast cancer (BC) is one of the commonest female cancers, which is characterized with high incidence. Although treatments have been improved, the prognosis of BC patients in advanced stages remains unsatisfactory. Thus, exploration of the molecular mechanisms underneath BC progression is necessary to find novel therapeutic methods. Frizzled class receptor (FZD2) belongs to Frizzled family, which has been proven to promote cell growth and invasion in various human cancers. The purpose of our study was to detect the functions of FZD2 and explore its mechanism in BC. Methods The level of FZD2 was measured in BC tissues by quantitative realtime polymerase chain reaction (qRT-PCR), western blot, immunohistochemistry (IHC) respectively. Cell Counting Kit-8 (CCK-8), standard colony formation, transwell aasays, wound healing and flow cytometry experiments were adopted separately to test cell viability, invasion, migration, apoptosis and cell cycle distribution. Epithelial-mesenchymal transition (EMT) biomarker were determined by using Immunofluorescence assay. Xenograft tumorigenicity assay was performed to assess the effect of FZD2 on tumor growth in vivo. Results We determined that FZD2 mRNA and protein expression was abundant in BC tissues. Moreover, high level of FZD2 had significant correlation with poor prognosis. In vitro functional assays revealed that silencing of FZD2 had suppressive effects on BC cell growth, migration and invasion. Animal study further demonstrated that FZD2 silencing inhibited BC cell growth in vivo. In addition, FZD2 induced EMT in BC cells in a transforming growth factor (TGF)-β1-dependent manner. Mechanistically, knockdown of FZD2 led to the inactivation of Notch signaling pathway. Conclusion Based on all these data, we concluded that FZD2 facilitates BC progression and promotes TGF-β1-inudced EMT process through activating Notch signaling pathway.

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FZD2 promotes TGF-β-induced epithelial-to-mesenchymal transition in breast cancer via activating notch signaling pathway

Cancer Cell International ◽

10.1186/s12935-021-01866-3 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Dilihumaer Tuluhong ◽

Tao Chen ◽

Jingjie Wang ◽

Huijuan Zeng ◽

Hanjun Li ◽

...

Keyword(s):

Breast Cancer ◽

Cell Growth ◽

Notch Signaling ◽

Signaling Pathway ◽

Notch Signaling Pathway ◽

Cell Counting ◽

Dependent Manner ◽

Mesenchymal Transition ◽

Tgf Β1

Abstract Background Breast cancer (BC) is one of the commonest female cancers, which is characterized with high incidence. Although treatments have been improved, the prognosis of BC patients in advanced stages remains unsatisfactory. Thus, exploration of the molecular mechanisms underneath BC progression is necessary to find novel therapeutic methods. Frizzled class receptor 2 (FZD2) belongs to Frizzled family, which has been proven to promote cell growth and invasion in various human cancers. The purpose of our current study was to detect the functions of FZD2 in BC and explore its underlying molecular mechanism. Methods The level of FZD2 was measured in BC tissues by quantitative real-time polymerase chain reaction (qRT-PCR), western blot, immunohistochemistry (IHC), respectively. Cell Counting Kit-8 (CCK-8), colony formation assay, transwell assays, wound healing assay and flow cytometry analyses were separately conducted to detect cell viability, invasion, migration, apoptosis and cell cycle distribution. The levels of Epithelial-mesenchymal transition (EMT) biomarkers were examined by using Immunofluorescence assay. Xenograft tumorigenicity assay was performed to assess the effect of FZD2 on tumor growth in vivo. Results FZD2 mRNA and protein expression was abundant in BC tissues. Moreover, high level of FZD2 had significant correlation with poor prognosis in BC patients. In vitro functional assays revealed that silencing of FZD2 had suppressive effects on BC cell growth, migration and invasion. Animal study further demonstrated that FZD2 silencing inhibited BC cell growth in vivo. In addition, FZD2 induced EMT process in BC cells in a transforming growth factor (TGF)-β1-dependent manner. Mechanistically, knockdown of FZD2 led to the inactivation of Notch signaling pathway. Conclusion FZD2 facilitates BC progression and promotes TGF-β1-inudced EMT process through activating Notch signaling pathway.

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FZD2 Promotes TGF-β-induced Epithelial-to-Mesenchymal Transition in Breast Cancer via Activating Notch Signaling Pathway

10.21203/rs.3.rs-63207/v3 ◽

2020 ◽

Author(s):

Dilihumaer Tuluhong ◽

Tao Chen ◽

Jingjie Wang ◽

Huijuan Zeng ◽

Hanjun Li ◽

...

Keyword(s):

Breast Cancer ◽

Cell Growth ◽

Notch Signaling ◽

Signaling Pathway ◽

Notch Signaling Pathway ◽

Cell Counting ◽

Dependent Manner ◽

Mesenchymal Transition ◽

Tgf Β1

Abstract Background: Breast cancer (BC) is one of the commonest female cancers, which is characterized with high incidence. Although treatments have been improved, the prognosis of BC patients in advanced stages remains unsatisfactory. Thus, exploration of the molecular mechanisms underneath BC progression is necessary to find novel therapeutic methods. Frizzled class receptor (FZD2) belongs to Frizzled family, which has been proven to promote cell growth and invasion in various human cancers. The purpose of our study was to detect the functions of FZD2 and explore its mechanism in BC.Methods: The level of FZD2 was measured in BC tissues by quantitative real-time polymerase chain reaction (qRT-PCR), western blot, immunohistochemistry (IHC) respectively. Cell Counting Kit-8 (CCK-8), colony formation assay, transwell assays, wound healing assay and flow cytometry analyses were conducted separately to test cell viability, invasion, migration, apoptosis and cell cycle distribution. Epithelial-mesenchymal transition (EMT) biomarkers were determined by using Immunofluorescence assay. Xenograft tumorigenicity assay was performed to assess the effect of FZD2 on tumor growth in vivo.Results: FZD2 mRNA and protein expression was abundant in BC tissues. Moreover, high level of FZD2 had significant correlation with poor prognosis. In vitro functional assays revealed that silencing of FZD2 had suppressive effects on BC cell growth, migration and invasion. Animal study further demonstrated that FZD2 silencing inhibited BC cell growth in vivo. In addition, FZD2 induced EMT in BC cells in a transforming growth factor (TGF)-β1-dependent manner. Mechanistically, knockdown of FZD2 led to the inactivation of Notch signaling pathway.Conclusion: FZD2 facilitates BC progression and promotes TGF-β1-inudced EMT process through activating Notch signaling pathway.

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FZD2 Promotes TGF-β-induced Epithelial-to-Mesenchymal Transition in Breast Cancer via Activating Notch Signaling Pathway

10.21203/rs.3.rs-63207/v2 ◽

2020 ◽

Author(s):

Dilihumaer Tuluhong ◽

Tao Chen ◽

Jingjie Wang ◽

Huijuan Zeng ◽

Hanjun Li ◽

...

Keyword(s):

Breast Cancer ◽

Cell Growth ◽

Notch Signaling ◽

Signaling Pathway ◽

Notch Signaling Pathway ◽

Cell Counting ◽

Dependent Manner ◽

Mesenchymal Transition ◽

Tgf Β1

Abstract Background Breast cancer (BC) is one of the commonest female cancers, which is characterized with high incidence. Although treatments have been improved, the prognosis of BC patients in advanced stages remains unsatisfactory. Thus, exploration of the molecular mechanisms underneath BC progression is necessary to find novel therapeutic methods. Frizzled class receptor (FZD2) belongs to Frizzled family, which has been proven to promote cell growth and invasion in various human cancers. The purpose of our study was to detect the functions of FZD2 and explore its mechanism in BC. Methods The level of FZD2 was measured in BC tissues by quantitative realtime polymerase chain reaction (qRT-PCR), western blot, immunohistochemistry (IHC) respectively. Cell Counting Kit-8 (CCK-8), standard colony formation, transwell aasays, wound healing and flow cytometry experiments were adopted separately to test cell viability, invasion, migration, apoptosis and cell cycle distribution. Epithelial-mesenchymal transition (EMT) biomarker were determined by using Immunofluorescence assay. Xenograft tumorigenicity assay was performed to assess the effect of FZD2 on tumor growth in vivo . Results We determined that FZD2 mRNA and protein expression was abundant in BC tissues. Moreover, high level of FZD2 had significant correlation with poor prognosis. In vitro functional assays revealed that silencing of FZD2 had suppressive effects on BC cell growth, migration and invasion. Animal study further demonstrated that FZD2 silencing inhibited BC cell growth in vivo. In addition, FZD2 induced EMT in BC cells in a transforming growth factor (TGF)-β1-dependent manner. Mechanistically, knockdown of FZD2 led to the inactivation of Notch signaling pathway. Conclusion Based on all these data, we concluded that FZD2 facilitates BC progression and promotes TGF-β1-inudced EMT process through activating Notch signaling pathway.

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Xia, J.; et al., Arsenic Trioxide Inhibits Cell Growth and Induces Apoptosis through Inactivation of Notch Signaling Pathway in Breast Cancer. Int. J. Mol. Sci. 2012, 13, 9627–9641

International Journal of Molecular Sciences ◽

10.3390/ijms150814907 ◽

2014 ◽

Vol 15 (8) ◽

pp. 14907-14908

Author(s):

Jun Xia ◽

Youjian Li ◽

Qingling Yang ◽

Chuanzhong Mei ◽

Zhiwen Chen ◽

...

Keyword(s):

Breast Cancer ◽

Cell Growth ◽

Notch Signaling ◽

Arsenic Trioxide ◽

Signaling Pathway ◽

Notch Signaling Pathway

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Emodin suppresses TGF-β1-induced epithelial-mesenchymal transition in alveolar epithelial cells through Notch signaling pathway

Toxicology and Applied Pharmacology ◽

10.1016/j.taap.2016.12.009 ◽

2017 ◽

Vol 318 ◽

pp. 1-7 ◽

Cited By ~ 14

Author(s):

Rundi Gao ◽

Ruilin Chen ◽

Yu Cao ◽

Yuan Wang ◽

Kang Song ◽

...

Keyword(s):

Epithelial Cells ◽

Notch Signaling ◽

Signaling Pathway ◽

Epithelial Mesenchymal Transition ◽

Notch Signaling Pathway ◽

Alveolar Epithelial Cells ◽

Mesenchymal Transition ◽

Alveolar Epithelial ◽

Tgf Β1

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3,6-dihydroxyflavone suppresses the epithelial-mesenchymal transition in breast cancer cells by inhibiting the Notch signaling pathway

Scientific Reports ◽

10.1038/srep28858 ◽

2016 ◽

Vol 6 (1) ◽

Cited By ~ 8

Author(s):

Junli Chen ◽

Hui Chang ◽

Xiaoli Peng ◽

Yeyun Gu ◽

Long Yi ◽

...

Keyword(s):

Breast Cancer ◽

Notch Signaling ◽

Cancer Cells ◽

Signaling Pathway ◽

Breast Cancer Cells ◽

Epithelial Mesenchymal Transition ◽

Notch Signaling Pathway ◽

Mesenchymal Transition

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NCSTN promotes hepatocellular carcinoma cell growth and metastasis via β-catenin activation in a Notch1/AKT dependent manner

10.21203/rs.3.rs-18622/v1 ◽

2020 ◽

Author(s):

Hui Li ◽

Tian Lan ◽

Lin Xu ◽

Hailing Liu ◽

Jinju Wang ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Cell Growth ◽

Nuclear Translocation ◽

Cell Counting ◽

Migration And Invasion ◽

Dependent Manner ◽

Mesenchymal Transition ◽

Gsk 3Β

Abstract Background Hepatocellular carcinoma is the third top cause of cancer-related mortalities worldwide. The prognosis of HCC patients remains poor due to rapid progression and high incidence of tumor recurrence. Nicastrin (NCSTN), a core subunit of γ-Secretase, has been reported to play a vital role in tumor progression. However, no study till now has revealed its role in HCC. Methods The expression of NCSTN was evaluated by immunohistochemical staining, Western blot, and quantitative real-time PCR. Cell counting kit-8, colony formation and cell cycle assays were used for evaluating cell growth in vitro. Transwell and wound-healing assays were used for evaluating cell migration and invasion capacity. Immunofluorescence, subcellular protein fractionation and co-immunoprecipitation were used for location analysis of β-catenin. The in vivo functions of NCSTN were illustrated by xenograft tumor models. Results NCSTN was dramatically overexpressed in HCC compared to normal liver tissues. Elevated NCSTN expression level was significantly correlated to worse overall and recurrence-free survival of HCC patients. Enhanced NCSTN expression promoted HCC cell growth, migration and invasion in vitro and in vivo. Mechanistic investigations showed that NCSTN induced epithelial-mesenchymal transition (EMT) process via upregulation of Zeb1. Subsequently, we revealed that NCSTN facilitated nuclear translocation of β-catenin, a positive transcriptional regulator of Zeb1. Using Notch and AKT inhibitors, we revealed that NCSTN promoted β-catenin activation through Notch1 and AKT signaling pathway. NCSTN increased AKT and GSK-3β phosphorylation by cleavage of Notch1, which decreased GSK-3β/β-catenin complex. The inactivation of GSK-3β inhibited the β-catenin degradation and promoted nuclear translocation of β-catenin to initiate transcription of Zeb1, resulting in malignant phenotype. Conclusions Our results demonstrated that NCSTN promoted HCC cell growth and metastasis via β-catenin-mediated upregulation of Zeb1 in a Notch1/AKT dependent manner, suggesting that NCSTN might serve as a potential prognostic marker and therapeutic target for HCC.

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