Oleic acid stimulates cell proliferation and BRD4–L-MYC-dependent glucose transporter transcription through PPARα activation in ovarian cancer cells

Kado, Tsuyoshi; Kusakari, Naoki; Tamaki, Takeru; Murota, Kazuo; Tsujiuchi, Toshifumi; Fukushima, Nobuyuki

doi:10.1016/j.bbrc.2023.03.051

Cited by 5 publications

(3 citation statements)

References 41 publications

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“…Exogenous supplementation with OA-inhibited Her-2/neu overexpression and cell proliferation, and synergistically enhanced trastuzumab-induced inhibition of cell growth and apoptosis in breast cancer cells with Her-2/neu amplification [35]. By contrast, 30 µM OA promoted cell proliferation and enhanced glycolytic activity through activation of peroxisome proliferator activated receptor α (PPARα) and the BRAD4-L-MYC-GLUT axis in ovarian cancer cells [29]. Treatment of OA at a dose of 100 µM stimulated cell viability, increased GPR40 expression, and effectively sensitized breast cancer cells to OA.…”

Section: Discussionmentioning

confidence: 99%

“…Long-term feeding with an OA-enriched diet reduced tumor diameter, increased tumor latency, and improved survival in a murine model of lung adenocarcinoma without affecting the incidence of pulmonary metastasis when compared with the mice fed a standard diet [21,28]. By contrast, OA at a dose of 30 µM increased cell proliferation and activated glycolysis through enhanced glucose transporter (GLUT) expression and activated peroxisome proliferator activated receptor (PPARa) in ovarian cancer cells [29]. Supplementation of OA in cervical cancer cells effectively stimulated cell proliferation, migration, and invasion through the FA transporter CD36 in a dose-dependent manner, and a high olive oil diet promoted tumor growth and metastasis in a mouse xenograft model of cervical cancer, indicating that increased intracellular OA concentrations and altered lipid pool composition may contribute to these OA-induced effects [30].…”

Section: Introductionmentioning

confidence: 99%

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Oleic Acid Exhibits Anti-Proliferative and Anti-Invasive Activities via the PTEN/AKT/mTOR Pathway in Endometrial Cancer

Deng,

Kong,

Suo

et al. 2023

Cancers

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Reprogramming of fatty acid metabolism promotes cell growth and metastasis through a variety of processes that stimulate signaling molecules, energy storage, and membrane biosynthesis in endometrial cancer. Oleic acid is one of the most important monounsaturated fatty acids in the human body, which appears to have both pro- and anti-tumorigenic activities in various pre-clinical models. In this study, we evaluated the potential anti-tumor effects of oleic acid in endometrial cancer cells and the LKB1fl/flp53fl/fl mouse model of endometrial cancer. Oleic acid increased lipogenesis, inhibited cell proliferation, caused cell cycle G1 arrest, induced cellular stress and apoptosis, and suppressed invasion in endometrial cancer cells. Targeting of diacylglycerol acyltransferases 1 and 2 effectively increased the cytotoxicity of oleic acid. Moreover, oleic acid significantly increased the expression of wild-type PTEN, and knockdown of PTEN by shRNA partially reversed the anti-proliferative and anti-invasive effects of oleic acid. Inhibition of the AKT/mTOR pathway by ipatasertib effectively increased the anti-tumor activity of oleic acid in endometrial cancer cells. Oleic acid treatment (10 mg/kg, daily, oral) for four weeks significantly inhibited tumor growth by 52.1% in the LKB1fl/flp53fl/fl mice. Our findings demonstrated that oleic acid exhibited anti-tumorigenic activities, dependent on the PTEN/AKT/mTOR signaling pathway, in endometrial cancer.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Oleic Acid Exhibits Anti-Proliferative and Anti-Invasive Activities via the PTEN/AKT/mTOR Pathway in Endometrial Cancer

Deng,

Kong,

Suo

et al. 2023

Cancers

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show abstract

“… Colorectal cancer Cell line and animal model Oleic acid-induced NOX4 is dependent on ANGPTL4 expression to promote human colorectal cancer metastasis [27] . Ovarian cancer Cell line Stimulate ovarian cancer cell proliferation by activating PPARα [28] . Prostate cancer Cell line Promote the malignant phenotype of prostate cancer through G protein-coupled receptor FFA1/GPR40 [29] .…”

Section: Resultsmentioning

confidence: 99%

DPP3 promotes breast cancer tumorigenesis by stabilizing FASN and promoting lipid synthesis

Fu,

Li,

Wang

et al. 2024

ABBS

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DPP3, a dipeptidyl peptidase, participates in a variety of pathophysiological processes. DPP3 is upregulated in cancer and might serve as a key factor in the tumorigenesis and progression of various malignancies. However, its specific role and molecular mechanism are still unknown. In this study, the expression of DPP3 in breast cancer tissues is analyzed using TCGA database. Kaplan-Meier survival analysis is performed to estimate the effect of DPP3 on the survival outcomes. To explore the biological function and mechanisms of DPP3 in breast cancer, biochemical and cell biology assays are conducted in vitro . DPP3 expresses at a higher level in breast cancer tissues than that in adjacent tissues in both TCGA database and clinical samples. Patients with high expression of DPP3 have poor survival outcomes. The proliferation and migration abilities of tumor cells with stable DPP3 knockout in breast cancer cell lines are significantly inhibited, and apoptosis is increased in vitro . GSEA analysis shows that DPP3 can affect lipid metabolism and fatty acid synthesis in tumors. Subsequent experiments show that DPP3 could stabilize FASN expression and thus promote fatty acid synthesis in tumor cells. The results of the metabolomic analysis also confirm that DPP3 can affect the content of free fatty acids. This study demonstrates that DPP3 plays a role in the reprogramming of fatty acid metabolism in tumors and is associated with poor prognosis in breast cancer patients. These findings will provide a new therapeutic target for the treatment of breast cancer.

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Phosphocholine inhibits proliferation and reduces stemness of endometrial cancer cells by downregulating mTOR-c-Myc signaling

Gong,

Zheng,

Liu

et al. 2024

Cell. Mol. Life Sci.

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Background Endometrial cancer (EC) represents a serious health concern among women globally. Excessive activation of the protooncogene c-Myc (c-Myc) is associated with the proliferation and stemness of EC cells. Phosphocholine (PC), which is synthesized by choline kinase alpha (CHKA) catalysis, is upregulated in EC tumor tissues. The present study aimed to investigate the effect of PC accumulation on EC cells and clarify the relationship between PC accumulation and c-Myc activity in EC. Methods The c-Myc and CHKA expression in EC tumor tissues were examined using immunohistochemistry. Cell Counting Kit-8 assay, colony formation assay, flow cytometry, western blotting, BrdU staining, and tumorsphere formation assay were used to assess the effect of PC accumulation on EC cells. The mechanism by which PC accumulation inhibits c-Myc was evaluated using RNA-sequencing. Patient-derived organoid (PDO) models were utilised to explore the preclinical efficacy of PC against EC cells. Results PC accumulation suppressed EC cell proliferation and stemness by inhibiting the activation of the mammalian target of rapamycin (mTOR)-c-Myc signaling. PC accumulation promoted excessive reactive oxygen species production, which reduced the expression of GTPase HRAS. This, in turn, inhibited the mTOR-c-Myc axis and induced EC cell apoptosis. Finally, PC impeded proliferation and downregulated the expression of the mTOR–MYC signaling in EC PDO models. Conclusions PC accumulation impairs the proliferation ability and stem cell characteristics of EC cells by inhibiting the activated mTOR-c-Myc axis, potentially offering a promising strategy to enhance the efficacy of EC clinical therapy through the promotion of PC accumulation in tumor cells. Supplementary Information The online version contains supplementary material available at 10.1007/s00018-024-05517-4.

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Oleic acid stimulates cell proliferation and BRD4–L-MYC-dependent glucose transporter transcription through PPARα activation in ovarian cancer cells

Cited by 5 publications

References 41 publications

Oleic Acid Exhibits Anti-Proliferative and Anti-Invasive Activities via the PTEN/AKT/mTOR Pathway in Endometrial Cancer

Oleic Acid Exhibits Anti-Proliferative and Anti-Invasive Activities via the PTEN/AKT/mTOR Pathway in Endometrial Cancer

DPP3 promotes breast cancer tumorigenesis by stabilizing FASN and promoting lipid synthesis

Phosphocholine inhibits proliferation and reduces stemness of endometrial cancer cells by downregulating mTOR-c-Myc signaling

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