Lysophosphatidic acid suppresses apoptosis of high-grade serous ovarian cancer cells by inducing autophagy activity and promotes cell-cycle progression via EGFR-PI3K/Aurora-AThr288-geminin dual signaling pathways

Zhao, Haile; Jia, Peijun; Nanding, Kathleen; Wu, Man; Bai, Xiaozhou; Fan, Lifei

doi:10.3389/fphar.2022.1046269

Cited by 2 publications

(2 citation statements)

References 99 publications

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“…LPA is also critically involved in the regulation of cell cycles and proliferation. LPA, via LPAR1 and 3, activates the epidermal growth factor receptor (EGFR)/PI3K/mammalian target of rapamycin (mTOR) and Aurora kinase pathways to promote geminin expression and stabilisation, which subsequently regulate DNA replication, cell cycle progression and proliferation of ovarian cancer cells [107]. A similar mechanism of LPA/geminincontrolled cell cycle progression has also been described in gastric cancer cells [108].…”

Section: Lpa In Proliferationmentioning

confidence: 87%

The Emerging Role of LPA as an Oncometabolite

Karalis,

Poulogiannis

2024

Cells

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Lysophosphatidic acid (LPA) is a phospholipid that displays potent signalling activities that are regulated in both an autocrine and paracrine manner. It can be found both extra- and intracellularly, where it interacts with different receptors to activate signalling pathways that regulate a plethora of cellular processes, including mitosis, proliferation and migration. LPA metabolism is complex, and its biosynthesis and catabolism are under tight control to ensure proper LPA levels in the body. In cancer patient specimens, LPA levels are frequently higher compared to those of healthy individuals and often correlate with poor responses and more aggressive disease. Accordingly, LPA, through promoting cancer cell migration and invasion, enhances the metastasis and dissemination of tumour cells. In this review, we summarise the role of LPA in the regulation of critical aspects of tumour biology and further discuss the available pre-clinical and clinical evidence regarding the feasibility and efficacy of targeting LPA metabolism for effective anticancer therapy.

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Section: Lpa In Proliferationmentioning

confidence: 87%

The Emerging Role of LPA as an Oncometabolite

Karalis,

Poulogiannis

2024

Cells

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“…The absence of NDUFA10, a vital subunit of mitochondrial complex I, leads to functional deficiency of the complex, which results in mitochondrial impairment [56]. Previous studies have also found an association between NDUFA10 and several diseases, such as nonalcoholic steatohepatitis [57], type 2 diabetes [58], Alzheimer's disease [59] and Leigh disease [38]. According to a previous study, decreased levels of NDUFA10 protein impair mitochondrial function, increase mitochondrial ROS production, and ultimately lead to disruption of cardiac structure and function [60].…”

Section: Discussionmentioning

confidence: 99%

CAV3 alleviates diabetic cardiomyopathy via inhibiting NDUFA10-mediated mitochondrial dysfunction

Guo,

Hu,

Liu

et al. 2024

J Transl Med

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Background The progression of diabetic cardiomyopathy (DCM) is noticeably influenced by mitochondrial dysfunction. Variants of caveolin 3 (CAV3) play important roles in cardiovascular diseases. However, the potential roles of CAV3 in mitochondrial function in DCM and the related mechanisms have not yet been elucidated. Methods Cardiomyocytes were cultured under high-glucose and high-fat (HGHF) conditions in vitro, and db/db mice were employed as a diabetes model in vivo. To investigate the role of CAV3 in DCM and to elucidate the molecular mechanisms underlying its involvement in mitochondrial function, we conducted Liquid chromatography tandem mass spectrometry (LC–MS/MS) analysis and functional experiments. Results Our findings demonstrated significant downregulation of CAV3 in the cardiac tissue of db/db mice, which was found to be associated with cardiomyocyte apoptosis in DCM. Importantly, cardiac-specific overexpression of CAV3 effectively inhibited the progression of DCM, as it protected against cardiac dysfunction and cardiac remodeling associated by alleviating cardiomyocyte mitochondrial dysfunction. Furthermore, mass spectrometry analysis and immunoprecipitation assays indicated that CAV3 interacted with NDUFA10, a subunit of mitochondrial complex I. CAV3 overexpression reduced the degradation of lysosomal pathway in NDUFA10, restored the activity of mitochondrial complex I and improved mitochondrial function. Finally, our study demonstrated that CAV3 overexpression restored mitochondrial function and subsequently alleviated DCM partially through NDUFA10. Conclusions The current study provides evidence that CAV3 expression is significantly downregulated in DCM. Upregulation of CAV3 interacts with NDUFA10, inhibits the degradation of lysosomal pathway in NDUFA10, a subunit of mitochondrial complex I, restores the activity of mitochondrial complex I, ameliorates mitochondrial dysfunction, and thereby protects against DCM. These findings indicate that targeting CAV3 may be a promising approach for the treatment of DCM.

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Lysophosphatidic acid suppresses apoptosis of high-grade serous ovarian cancer cells by inducing autophagy activity and promotes cell-cycle progression via EGFR-PI3K/Aurora-AThr288-geminin dual signaling pathways

Cited by 2 publications

References 99 publications

The Emerging Role of LPA as an Oncometabolite

The Emerging Role of LPA as an Oncometabolite

CAV3 alleviates diabetic cardiomyopathy via inhibiting NDUFA10-mediated mitochondrial dysfunction

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