Mitofusin 2 inhibits bladder cancer cell proliferation and invasion via the Wnt/β‑catenin pathway

Pang, Guofu; Xie, Qun; Yao, Juanjuan

doi:10.3892/ol.2019.10570

Cited by 21 publications

(27 citation statements)

References 26 publications

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“…The Wnt/β-catenin signaling pathway has been under attention in recent years due to its role in tumorigenesis [ 115 , 116 , 117 , 118 , 119 ]. The tumor-promoting role of Wnt signaling pathway has been investigated in different cancers, including BC [ 120 , 121 ]. It has been found that Wnt signaling can act as an upstream mediator of EMT, so that after activation of Wnt signaling pathway by certain ligands of Wnt family, GSK-3β activity can be inhibited to facilitate the nuclear translocation of β-catenin.…”

Section: Micrornas Inhibit Emt In Bladder Cancer Cellsmentioning

confidence: 99%

Role of microRNA/Epithelial-to-Mesenchymal Transition Axis in the Metastasis of Bladder Cancer

et al. 2020

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Bladder cancer (BC) is the 11th most common diagnosed cancer, and a number of factors including environmental and genetic ones participate in BC development. Metastasis of BC cells into neighboring and distant tissues significantly reduces overall survival of patients with this life-threatening disorder. Recently, studies have focused on revealing molecular pathways involved in metastasis of BC cells, and in this review, we focus on microRNAs (miRNAs) and their regulatory effect on epithelial-to-mesenchymal transition (EMT) mechanisms that can regulate metastasis. EMT is a vital process for migration of BC cells, and inhibition of this mechanism restricts invasion of BC cells. MiRNAs are endogenous non-coding RNAs with 19–24 nucleotides capable of regulating different cellular events, and EMT is one of them. In BC cells, miRNAs are able to both induce and/or inhibit EMT. For regulation of EMT, miRNAs affect different molecular pathways such as transforming growth factor-beta (TGF-β), Snail, Slug, ZEB1/2, CD44, NSBP1, which are, discussed in detail this review. Besides, miRNA/EMT axis can also be regulated by upstream mediators such as lncRNAs, circRNAs and targeted by diverse anti-tumor agents. These topics are also discussed here to reveal diverse molecular pathways involved in migration of BC cells and strategies to target them to develop effective therapeutics.

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Section: Micrornas Inhibit Emt In Bladder Cancer Cellsmentioning

confidence: 99%

Role of microRNA/Epithelial-to-Mesenchymal Transition Axis in the Metastasis of Bladder Cancer

et al. 2020

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“…Many studies have shown that ERβ is an anti-oncogene in breast cancer and that the loss of ERβ may promote breast cancer occurrence (19,20). As a novel tumor suppressor gene, MFN2 is related to the antitumor activity of many malignant tumors (21)(22)(23). No other studies have provided detailed data or have investigated the effect of ERβ on MFN2 and P-AKT expression in breast cancer.…”

Section: Discussionmentioning

confidence: 99%

“…Recently, promising data have been obtained for the development of PI3K/AKT inhibitors in breast cancer and have provided a theoretical basis for the development of PI3K/AKT-targeted inhibitors (36). Although many studies have been performed to determine the relationship between the AKT pathway and breast cancer in recent years (21)(22)(23), none of these studies has demonstrated that the P-AKT signaling pathway is downstream of ERβ/MFN2. Our data indicated that in MCF-7 and MDA-MB-231 human breast cancer cells, ERβ induced the expression of MFN2, while MFN2 reduced P-AKT, and P-AKT was downstream of ERβ/MFN2.…”

Section: Discussionmentioning

confidence: 99%

ERβ-induced MFN2 inhibits the migration and invasiveness of breast cancer cells by inhibiting the P-AKT signaling pathway

Hao

Liao

Liu

et al. 2020

Preprint

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Background Mitofusin 2 (MFN2) is localized on the outer membrane of mitochondria and is closely related to the migration of malignant tumor cells. Estrogen receptor β (ERβ) plays an anticancer role in breast cancer. Our previous experiments showed that ERβ can induce MFN2 expression, which then inhibits breast cancer cell migration. However, the exact mechanism by which ERβ-induced MFN2 inhibits breast cancer cell migration is unknown. Methods In this study, immunohistochemistry was first used to detect the expression of MFN2 in breast cancer tissues, and its relationship with the clinicopathological characteristics and prognosis of breast cancer patients was analyzed. MCF-7 and MDA-MB-231 cells were transfected with ERβ and MFN2 knockdown or expression plasmids. Western blot was used to detect the effects of ERβ on MFN2 and MFN2 on P-AKT473 and MMP2; the P-AKT pathway inhibitor LY294002 was administered to cells transfected with MFN2 knockdown plasmids, Western blot, immunocytofluorescence, and a wound healing assay revealed the effect of MFN2 on its downstream signaling pathway and the migration of breast cancer cells. Results This study found that the expression of MFN2 is related to the molecular type and prognosis of breast cancer patients ( P <0.05). The positive expression rate of MFN2 in triple-negative breast cancer was significantly lower than that in the HER2 + and luminal types. However, MFN2 expression was unrelated to age, tumor size, lymph node metastasis, TNM stage, histological type and grade ( P >0.05); ERβ positively regulated MFN2 expression and reduced the migration of both MCF-7 and MDA-MB-231 cells, while MFN2 knockdown increased the expression of P-AKT473 and MMP2. In contrast, the overexpression of MFN2 inhibited the expression of P-AKT473 and MMP2. These results showed that in MFN2 knockdown cells treated with LY294002, P-AKT473 and MMP2 expression levels were reversed. The reversal of P-AKT473 and MMP2 expression levels inhibits the invasiveness of human breast cancer cells. Conclusion MFN2 is related to the molecular subtype and prognosis of breast cancer. In human breast cancer MCF-7 and MDA-MB-231 cells, ERβ-induced MFN2 can inhibit the P-AKT pathway, which inhibits the invasiveness and migration of both breast cancer cell lines.

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“…In patients suffering from gastric cancers, a significant increase in the expression of YAP and β-catenin has been correlated to the disease severity [65]. An activation of Wnt/β-catenin signaling has also been associated with the development of colorectal cancer [66], glioblastoma [67] and bladder cancer [68] in patients. Considering the importance of this signaling in different cancers, a Phase II trial has been designed to investigate the safety and efficacy of oral niclosamide, Wnt/β-catenin signaling modulating drug, in colorectal cancer patients [69].…”

Section: Discussionmentioning

confidence: 99%

Wnt/β-catenin signaling as a useful therapeutic target in hepatoblastoma

et al. 2019

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Hepatoblastoma is a malignant tumor in the liver of children that generally occurs at the age of 2–3 years. There have been ample evidence from the preclinical as well as clinical studies suggesting the activation of Wnt/β-catenin signaling in hepatoblastoma, which is mainly attributed to the somatic mutations in the exon 3 of β-catenin gene. There is increased translocation of β-catenin protein from the cell surface to cytoplasm and nucleus and intracellular accumulation is directly linked to the severity of the cancer. Accordingly, the alterations in β-catenin and its target genes may be used as markers in the diagnosis and prognosis of pediatric live tumors. Furthermore, scientists have reported the therapeutic usefulness of inhibition of Wnt/β-catenin signaling in hepatoblastoma and this inhibition of signaling has been done using different methods including short interfering RNA (siRNA), miRNA and pharmacological agents. Wnt/β-catenin works in association with other signaling pathways to induce the development of hepatoblastoma including Yes-associated protein (YAP)1 (YAP-1), mammalian target of rapamycin (mTOR) 1 (mTOR-1), SLC38A1, glypican 3 (GPC3), nuclear factor κ-light-chain-enhancer of activated B cells (NF-kB), epidermal growth factor receptor, ERK1/2, tumor necrosis factor-α (TNF-α), regenerating islet-derived 1 and 3 α (REG1A and 3A), substance P (SP)/neurokinin-1 receptor and PARP-1. The present review describes the key role of Wnt/β-catenin signaling in the development of hepatoblastoma. Moreover, the role of other signaling pathways in hepatoblastoma in association with Wnt/β-catenin has also been described.

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Mitofusin 2 inhibits bladder cancer cell proliferation and invasion via the Wnt/β‑catenin pathway

Cited by 21 publications

References 26 publications

Role of microRNA/Epithelial-to-Mesenchymal Transition Axis in the Metastasis of Bladder Cancer

Role of microRNA/Epithelial-to-Mesenchymal Transition Axis in the Metastasis of Bladder Cancer

ERβ-induced MFN2 inhibits the migration and invasiveness of breast cancer cells by inhibiting the P-AKT signaling pathway

Wnt/β-catenin signaling as a useful therapeutic target in hepatoblastoma

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