Pro-apoptotic and anti-proliferative effects of mitofusin-2 via PI3K/Akt signaling in breast cancer cells

I, L; Chang, Yuan Yen; Yu, Ling; He, Wenbo; Liu, Yueping

doi:10.3892/ol.2015.3748

Cited by 33 publications

(28 citation statements)

References 25 publications

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“…Hence, the single loss of Mfn1 might have enhanced MFN2 activity, with potential deleterious consequences such as those observed in Mfn1 ‐cKO oocytes. In support of this notion, previous reports have shown that MFN2 inhibits the PI3K‐Akt signaling 17,56‐59 . In addition, overexpression of MFN2, but not MFN1, impairs ER redistribution and results in a severe loss of Ca 2+ stores in oocytes 5 .…”

Section: Discussionmentioning

confidence: 57%

Mitofusin 1 is required for oocyte growth and communication with follicular somatic cells

et al. 2020

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Mitochondrial function, largely regulated by the dynamics of this organelle, is inextricably linked to the oocyte health. In comparison with most somatic cells, mitochondria in oocytes are smaller and rounder in appearance, suggesting limited fusion. The functional implications of this distinct morphology, and how changes in the mitochondrial shape translate to mitochondrial function in oogenesis is little understood. We, therefore, asked whether the pro‐fusion proteins mitofusins 1 (MFN1) and 2 (MFN2) are required for the oocyte development. Here we show that oocyte‐specific deletion of Mfn1, but not Mfn2, prevents the oocyte growth and ovulation due to a block in folliculogenesis. We pinpoint the loss of oocyte growth and ovulation to impaired PI3K‐Akt signaling and disrupted oocyte‐somatic cell communication. In support, the double loss of Mfn1 and Mfn2 partially rescues the impaired PI3K‐Akt signaling and defects in oocyte development secondary to the single loss of Mfn1. Together, this work demonstrates that the mitochondrial function influences the cellular signaling during the oocyte development, and highlights the importance of distinct, nonredundant roles of MFN1 and MFN2 in oogenesis.

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Section: Discussionmentioning

confidence: 57%

Mitofusin 1 is required for oocyte growth and communication with follicular somatic cells

et al. 2020

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“…24) Furthermore, bavachin was reported to exhibit direct effect on Akt phosphorylation. 11,57) In this study, we showed that Mfn2 ablation by the siRNA resulted in the inhibition of phosphor-Akt, and inhibition of phosphorAkt also aggravated bavachin-induced ER stress (Fig. S1).…”

Section: Discussionmentioning

confidence: 95%

Bavachin Induces Apoptosis through Mitochondrial Regulated ER Stress Pathway in HepG2 Cells

Yang

Tang²,

Hao³

et al. 2018

Biological & Pharmaceutical Bulletin

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As a traditional herbal medicine, the fruits of Psoralea corylifolia L. (Fructus Psoraleae (FP)) have been widely used for the treatment of various skin diseases for hundred years. Recently, the emerging FPinduced toxic effects, especially hepatotoxicity, in clinic are getting the public's attention. However, its exact toxic components and mechanisms underlying remain unclear. Bavachin, one of flavonoids in FP, has been documented as a hepatotoxic substance, and the present study aimed to determine the toxicity caused by bavachin and the possible toxic mechanisms involved using human hepatocellular carcinoma (HepG2) cells. Our results showed that bavachin could significantly inhibited cell proliferation and trigger the endoplasmic reticulum (ER) stress in a dose dependent manner. Downregulating ER stress using tauroursodeoxycholic acid (TUDCA) obvious attenuated bavachin-triggerd cell apoptosis. Then, small interfering RNA (siRNA) knock-down of Mitofusion2 (Mfn2) resulted in a remarkable aggravation of ER stress through the inhibition of the phosphorylation of protein kinase B (Akt). Additionally, suppression of reactive oxygen species (ROS) by ROS Scavenger (N-acetyl-l-cystein (NAC)) also reduced bavachin-induced ER stress. Taken together, our study demonstrated that bavachin-induced ER stress caused cell apoptosis by Mfn2-Akt pathway, and that ROS may participate upstream in this mechanism. Here, we not only provide a new understanding of ROS/ Mfn2/Akt pathway in bavachin-induced cytotoxicity via the ER stress, but also identify a new specific intervention to prevent FP-induced hepatotoxicity in the future.

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“…PI3K/Akt signaling pathway is aberrant in a wide variety of cancers and has been shown to play a central role in cancer cell proliferation, migration, invasion, and apoptosis [15][16][17]. Downstream effectors of AKT are involved in survival, growth and metabolic-related pathways [18].…”

Section: Discussionmentioning

confidence: 99%

Long non-coding RNA MALAT1 promotes cholangiocarcinoma cell proliferation and invasion by activating PI3K/Akt pathway

Wang¹,

Mao²,

Wang³

et al. 2017

neo

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Increasing evidence indicated that metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) acted as a key regulator in the proliferation and invasion of several cancers. However, the function of MALAT1 in the development of cholangiocarcinoma has not been experimentally established. In the present study, the expression levels of MALAT1 in cholangiocarcinoma cell lines were detected by quantitative real-time PCR. The effects of MALAT1 knockdown on the cell proliferation and invasion of cholangiocarcinoma cells were detected with Cell Counting Kit-8 (CCK-8), colony formation assay and Trans-well assay, respectively. The expressions of epithelial-mesenchymal transition (EMT)-related proteins (E-cadherin, Vimentin) were evaluated to discover whether the process of EMT was involved. We also evaluated the expression of phos-phatidylinositol-3-kinase/serine/threonine kinase (PI3K/Akt) signaling pathway proteins (PI3K, p-PI3K, Akt, p-Akt) to determine the associated molecular mechanism. And we discovered that MALAT1 was up-regulated in cholangiocarcinoma cancer cells. CCK-8, colony formation and trans-well assay showed that the proliferation and invasion of QBC-939 and RBE with MALAT1 knockdown were inhibited. Moreover, MALAT1 could promote EMT in cholangiocarcinoma cells. In addition, MALAT1 may activate PI3K/Akt pathway. These results indicated that MALAT1 promoted cholangiocarcinoma cell proliferation and invasion. The effects of MALAT1 on cholangiocarcinoma cells might be through activating the PI3K/Akt signaling pathway. These investigations may facilitate a better understanding of MALAT1 and it might be a potential therapeutic target for the treatment of cholangiocarcinoma.

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Pro-apoptotic and anti-proliferative effects of mitofusin-2 via PI3K/Akt signaling in breast cancer cells

Cited by 33 publications

References 25 publications

Mitofusin 1 is required for oocyte growth and communication with follicular somatic cells

Mitofusin 1 is required for oocyte growth and communication with follicular somatic cells

Bavachin Induces Apoptosis through Mitochondrial Regulated ER Stress Pathway in HepG2 Cells

Long non-coding RNA MALAT1 promotes cholangiocarcinoma cell proliferation and invasion by activating PI3K/Akt pathway

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