A TGF-β-MTA1-SOX4-EZH2 signaling axis drives epithelial–mesenchymal transition in tumor metastasis

Li, Lina; Liu, Jian; Xue, Hongsheng; Li, Chunxiao; Li, Qun; Zhou, Yantong; Wang, Ting; Wang, Haijuan; Qian, Haili; Wen, Tao

doi:10.1038/s41388-019-1132-8

Cited by 76 publications

(60 citation statements)

References 57 publications

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“…However, tumor metastasis involves numerous factors, such as cytokines and the internal microenvironment, and EMT may be one of the most important factors in the overall process (38). Tumor cells collected from bone metastases in patients with prostate, breast and colon cancer expressed EMT markers, and those with ovarian cancer showed EMT in the process of metastasis (39)(40)(41).…”

Section: Discussionmentioning

confidence: 99%

Laminin‑332 mediates proliferation, apoptosis, invasion, migration and epithelial‑to‑mesenchymal transition in pancreatic ductal adenocarcinoma

Huang

2020

Mol Med Rep

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The poor prognosis of patients with pancreatic ductal adenocarcinoma (PDAC) is primarily due to the invasive and metastatic behaviors of this disease. Laminin-332 (LM-332) is a key component of the basement membrane barrier, and is associated with tumor metastasis. The present study provides evidence towards the potential function of LM-332 in carcinoma, indicating the distinct roles of the three LM-332 subunits (α3, β3 and γ2) in cell proliferation, migration, invasion, apoptosis and the epithelial-to-mesenchymal transition (EMT) in cancer. The roles of the α3, β3 and γ2 subunits in the malignant biological behavior of PDAC were investigated in the present study. It was revealed that the α3, β3 and γ2 subunits were upregulated in PDAC. Inhibition of all LM-332 subunits abrogated the tumorigenic outcomes, which included cell proliferation, apoptosis, invasion, migration and EMT in vitro. However, the three LM-332 subunits had different degrees of effects on biological behavior. It was observed that LAMA3 (α3) had a stronger effect on cell proliferation, migration and invasion. In addition, LAMB3 (β3) knockdown significantly increased E-cadherin levels and decreased vimentin levels, indicating that LAMB3 was associated with EMT. Likewise, LAMC2 (γ2) mediated proliferation, apoptosis, invasion and migration. However, small interfering (si)-LAMC2 promoted the progression of EMT, which was the opposite effect to that of si-LAMB3. The LM-332 subunits (α3, β3 and γ2) may be novel therapeutic targets of PDAC in the future.

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Section: Discussionmentioning

confidence: 99%

Laminin‑332 mediates proliferation, apoptosis, invasion, migration and epithelial‑to‑mesenchymal transition in pancreatic ductal adenocarcinoma

Huang

2020

Mol Med Rep

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“…Metastasis is a complex process, which involves many genetic and epigenetic aberrations [6,7]. Several molecules and signaling pathways are involved in colon cancer metastatic processes, such as p53, APC, transforming growth factor-b, nuclear factor kappa B (NF-jB), and epithelial-to-mesenchymal transition [8][9][10][11]. As a crucial transcription factor involved in inflammation and carcinogenesis, NF-jB contains five main subunits p65, p50/p105, p52/p100, RelB, and c-Rel.…”

Section: Introductionmentioning

confidence: 99%

Long noncoding RNA LINC01578 drives colon cancer metastasis through a positive feedback loop with the NF‐κB/YY1 axis

et al. 2020

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Metastasis accounts for poor prognosis of cancers and related deaths. Accumulating evidence has shown that long noncoding RNAs (lncRNAs) play critical roles in several types of cancer. However, which lncRNAs contribute to metastasis of colon cancer is still largely unknown. In this study, we found that lncRNA LINC01578 was correlated with metastasis and poor prognosis of colon cancer. LINC01578 was upregulated in colon cancer, associated with metastasis, advanced clinical stages, poor overall survival, disease-specific survival, and disease-free survival. Gain-of-function and loss-of-function assays revealed that LINC01578 enhanced colon cancer cell viability and mobility in vitro and colon cancer liver metastasis in vivo. Mechanistically, nuclear factor kappa B (NF-jB) and Yin Yang 1 (YY1) directly bound to the LINC01578 promoter, enhanced its activity, and activated LINC01578 expression. LINC01578 was shown to be a chromatin-bound lncRNA, which directly bound NFKBIB promoter. Furthermore, LINC01578 interacted with and recruited EZH2 to NFKBIB promoter and further repressed NFKBIB expression, thereby activating NF-jB signaling. Through activation of NF-jB, LINC01578 further upregulated YY1 expression. Through activation of the NF-jB/YY1 axis, LINC01578 in turn enhanced its own promoter activity, suggesting that LINC01578 and NF-jB/YY1 formed a positive feedback loop. Blocking NF-jB signaling abolished the oncogenic roles of LINC01578 in colon cancer. Furthermore, the expression levels of LINC01578, NFKBIB, and YY1 were correlated in clinical tissues. Collectively, this study demonstrated that LINC01578 promoted colon cancer metastasis via forming a positive feedback loop with NF-jB/YY1 and suggested that LINC01578 represents a potential prognostic biomarker and therapeutic target for colon cancer metastasis.

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“…MTA1 acts as an oncogene in various cancers, 6 and promotes the process of cancer progression and metastasis by inducing EMT in epithelial cancers, 35 hepatocellular cancer, 36 non-small-cell lung cancer, 37 and other tumors. 38 , 39 , 40 Our previous studies have demonstrated that MTA1 is overexpressed in endometrial cancer and facilitates endometrial cancer cell proliferation, migration, and invasion.…”

Section: Discussionmentioning

confidence: 99%

“…Studies have revealed that MTA1 contributes to metastasis by promoting EMT in various cancers. 35 , 36 , 37 , 38 , 39 , 40 However, whether MTA1 promotes EMT in endometriosis remains unclear.…”

Section: Introductionmentioning

confidence: 99%

MTA1, a Target of Resveratrol, Promotes Epithelial-Mesenchymal Transition of Endometriosis via ZEB2

Kong

Zhou

et al. 2020

Molecular Therapy - Methods & Clinical Development

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Endometriosis is a benign disease that shares some malignant features. Epithelial-mesenchymal transition (EMT) is involved in the pathogenesis of endometriosis. Metastasis-associated protein 1 (MTA1) plays an important role in various cancers by promoting EMT, yet there are no studies on its function in endometriosis. In the present study, we found that MTA1 was highly expressed in the ectopic endometrium of endometriosis patients and that the expression of MTA1 was related to the revised American Fertility Society stage. MTA1 facilitated endometrial stroma cell proliferation, migration, and invasion by inducing EMT, and the promotion function and MTA1 expression were suppressed by resveratrol, a natural polyphenol. Moreover, we revealed that MTA1 induced EMT through interaction with ZEB2. The findings in a mouse endometriosis model further showed that MTA1 and ZEB2 were upregulated in ectopic tissues and that resveratrol inhibited the growth of ectopic lesions and expression of MTA1 and ZEB2. Taken together, we demonstrate that MTA1 is a protein that promotes EMT via interacting with ZEB2 in the pathogenesis of endometriosis, and may be a target of resveratrol.

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A TGF-β-MTA1-SOX4-EZH2 signaling axis drives epithelial–mesenchymal transition in tumor metastasis

Cited by 76 publications

References 57 publications

Laminin‑332 mediates proliferation, apoptosis, invasion, migration and epithelial‑to‑mesenchymal transition in pancreatic ductal adenocarcinoma

Laminin‑332 mediates proliferation, apoptosis, invasion, migration and epithelial‑to‑mesenchymal transition in pancreatic ductal adenocarcinoma

Long noncoding RNA LINC01578 drives colon cancer metastasis through a positive feedback loop with the NF‐κB/YY1 axis

MTA1, a Target of Resveratrol, Promotes Epithelial-Mesenchymal Transition of Endometriosis via ZEB2

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