c-Myb Enhances Breast Cancer Invasion and Metastasis through the Wnt/β-Catenin/Axin2 Pathway

Li, Yihao; Jin, Ke; Pelt, Gabi W. van; Dam, Hans van; Yu, Xiaobing; Mesker, Wilma E.; Dijke, Peter ten; Zhou, Fangfang; Zhang, Long

doi:10.1158/0008-5472.can-15-2302

Cited by 106 publications

(79 citation statements)

References 43 publications

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“…Wnt signaling pathway has been reported to be correlated with cancer cell metastasis 25. Our study also demonstrated that MLL1 interacted with β-catenin.…”

Section: Resultssupporting

confidence: 71%

MLL1 promotes cervical carcinoma cell tumorigenesis and metastasis through interaction with β-catenin

Qiang

Cai

Wang

et al. 2016

OTT

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MLL protein genes encode a family of crucial transcription factors that play a key role in multiple cancer development. The functions of different MLL proteins have not been definitively studied. MLL1 is a histone methyltransferase that mediates histone H3 lysine 4, and it has been found to have aberrant expression in several tumors. However, the function of MLL1 in cervical carcinoma is little known. We used tissue analysis, cell culture experiments, and molecular profiling to investigate the mechanism of MLL1 in cervical carcinoma development. We report here that MLL1 is overexpressed in cervical carcinoma tissues and cell lines, and its overexpression is correlated with the tumor grade. Through FACScan flow cytometry assay, we found that MLL1 promotes cell proliferation by promoting the G1/S transition through transcriptional activation of CCND1 in cervical carcinoma cells. Furthermore, we utilized co-immunoprecipitation and glutathione S-transferase pull-down assays to identify β-catenin as the transcription partner for MLL1 and demonstrated that MLL1 and β-catenin act in synergy in the transcriptional activation of CCND1 in cervical carcinoma cells. In addition, transwell assay and anchorage-independent cell growth assay also revealed that MLL1 promotes metastasis of cervical carcinoma cells through interaction with β-catenin. Our study not only demonstrated a role for MLL1 in the proliferation and metastasis of cervical carcinoma cells but also revealed the interaction of MLL1 with β-catenin to play a different role.

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“…Wnt signaling pathway has been reported to be correlated with cancer cell metastasis 25. Our study also demonstrated that MLL1 interacted with β-catenin.…”

Section: Resultssupporting

confidence: 71%

MLL1 promotes cervical carcinoma cell tumorigenesis and metastasis through interaction with β-catenin

Qiang

Cai

Wang

et al. 2016

OTT

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“…Moreover, we revealed that the activity of th Wnt/β-catenin signaling pathway was decreased after Prrx2 silenced by using the luciferas reporter assay system. Cyclin-D1 is one of the important target genes downstream of the Wnt/β-catenisignag pathway [25, 26], silencing of Prrx2 could significantly inhibit the expression of cyclin-D1. The above experiments revealed that Wnt/β-catenin signaling pathway may participate in Prrx2-induced EMT of breast cancer.…”

Section: Discussionmentioning

confidence: 99%

Silencing of Prrx2 Inhibits the Invasion and Metastasis of Breast Cancer both In Vitro and In Vivo by Reversing Epithelial-Mesenchymal Transition

Lv¹,

Wang

Liu

et al. 2017

Cell Physiol Biochem

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Background/Aims: Epithelial-mesenchymal transition (EMT) is recognized as a crucial mechanism in breast cancer progression and metastasis. Paired-related homeobox 2 (Prrx2) has been identified as a new EMT inducer in cancer, but the underlying mechanisms are still poorly understood. Methods: The expression of Prrx2 was assessed by immunohistochemistry in breast cancer tissues to evaluate the clinicopathological significance of Prrx2, as well as the correlation between Prrx2 and EMT. Short hairpin RNA knockdown of Prrx2 was used to examine cellular effects of Prrx2, detecte the expression of Wnt/β-catenin signaling and EMT-associated proteins, and observe cell proliferation, invasion and migration abilities in vitro and in vivo. Results: Clinical association studies showed that Prrx2 expression was related to tumor size, lymph node metastasis, tumor node metastasis stages, EMT and poor survival. Results also showed that knockdown of Prrx2 could alter cell morphology, suppressed the abilities of cell proliferation, invasion and migration in breast cancer. Moreover, silencing of Prrx2 induced the mesenchymal-epithelial transition and prevented nuclear translocation of β-catenin, inhibited wnt/β-catenin signaling pathway. Conclusion: Our study indicated that Prrx2 may be an important activator of EMT in human breast cancer and it can serve as a molecular target of therapeutic interventions for breast cancer.

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“…Experimental metastasis to the lungs was induced by injecting 0.2 × 10 6 cells in 100 μl of PBS in the tail vein of female athymic nude mice. Mouse nipple implantation of 4T1 cells was based on a previously published method49. Female BALB/c mice were anaesthetized and used for this assay.…”

Section: Methodsmentioning

confidence: 99%

FAF1 phosphorylation by AKT accumulates TGF-β type II receptor and drives breast cancer metastasis

Xie¹,

Jin²,

Shao

et al. 2017

Nat Commun

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TGF-β is pro-metastatic for the late-stage breast cancer cells. Despite recent progress, the regulation of TGF-β type II receptor remains uncertain. Here we report that FAF1 destabilizes TβRII on the cell surface by recruiting the VCP/E3 ligase complex, thereby limiting excessive TGF-β response. Importantly, activated AKT directly phosphorylates FAF1 at Ser 582, which disrupts the FAF1–VCP complex and reduces FAF1 at the plasma membrane. The latter results in an increase in TβRII at the cell surface that promotes both TGF-β-induced SMAD and non-SMAD signalling. We uncover a metastasis suppressing role for FAF1 through analyses of FAF1-knockout animals, various in vitro and in vivo models of epithelial-to-mesenchymal transition and metastasis, an MMTV-PyMT transgenic mouse model of mammary tumour progression and clinical breast cancer samples. These findings describe a previously uncharacterized mechanism by which TβRII is tightly controlled. Together, we reveal how SMAD and AKT pathways interact to confer pro-oncogenic responses to TGF-β.

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c-Myb Enhances Breast Cancer Invasion and Metastasis through the Wnt/β-Catenin/Axin2 Pathway

Cited by 106 publications

References 43 publications

MLL1 promotes cervical carcinoma cell tumorigenesis and metastasis through interaction with β-catenin

MLL1 promotes cervical carcinoma cell tumorigenesis and metastasis through interaction with β-catenin

Silencing of Prrx2 Inhibits the Invasion and Metastasis of Breast Cancer both In Vitro and In Vivo by Reversing Epithelial-Mesenchymal Transition

FAF1 phosphorylation by AKT accumulates TGF-β type II receptor and drives breast cancer metastasis

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c-Myb Enhances Breast Cancer Invasion and Metastasis through the Wnt/β-Catenin/Axin2 Pathway

Cited by 106 publications

References 43 publications

MLL1 promotes cervical carcinoma cell tumorigenesis and metastasis through interaction with &beta;-catenin

MLL1 promotes cervical carcinoma cell tumorigenesis and metastasis through interaction with &beta;-catenin

Silencing of Prrx2 Inhibits the Invasion and Metastasis of Breast Cancer both In Vitro and In Vivo by Reversing Epithelial-Mesenchymal Transition

FAF1 phosphorylation by AKT accumulates TGF-β type II receptor and drives breast cancer metastasis

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MLL1 promotes cervical carcinoma cell tumorigenesis and metastasis through interaction with β-catenin

MLL1 promotes cervical carcinoma cell tumorigenesis and metastasis through interaction with β-catenin