Cholesterol metabolism and lipid droplet vacuoles; a potential target for the therapy of aggressive lymphoma

Yano, Hiromichi; Fujiwara, Yukio; Komohara, Yoshihiro

doi:10.3960/jslrt.22023

Cited by 6 publications

(11 citation statements)

References 26 publications

(41 reference statements)

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“…It had been reported that LDLR promoted lung cancer cell growth and metastasis, 17 and accelerated breast carcinoma cell proliferation, 18 confirming the pro‐tumor role of LDLR. In this, we detected high LDLR expression in DLBCL, which was consistent with the previous study 10 . Besides, LDLR knockdown suppressed DLBCL cell proliferation and promoted ferroptosis, and its overexpression had an opposite effect.…”

Section: Discussionsupporting

confidence: 92%

“…In this, we detected high LDLR expression in DLBCL, which was consistent with the previous study. 10 Besides, LDLR knockdown suppressed DLBCL cell proliferation and promoted ferroptosis, and its overexpression had an opposite effect. In animal models, overexpressed LDLR enhanced DLBCL tumor growth by increasing tumor cell proliferation and decreasing ferroptosis.…”

Section: Paqr3 Inhibited Dlbcl Tumor Growth Via Promoting Ferroptosis...mentioning

confidence: 99%

“…9 Importantly, LDLR was found to be upregulated in lymphoma cells. 10 However, the role of LDLR in DLBCL progression remains unclear.…”

Section: Introductionmentioning

confidence: 99%

“…Besides, LDLR knockdown could repress renal cell carcinoma cell growth and metastasis 9 . Importantly, LDLR was found to be upregulated in lymphoma cells 10 . However, the role of LDLR in DLBCL progression remains unclear.…”

Section: Introductionmentioning

confidence: 99%

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PAQR3 facilitates the ferroptosis of diffuse large B‐cell lymphoma via the regulation of LDLR‐mediated PI3K/AKT pathway

Song,

Zhang,

et al. 2023

Hematological Oncology

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Progesterone and adiponectin receptor 3 (PAQR3) has been found to regulate tumor progression by mediating cell ferroptosis. However, whether PAQR3 mediates ferroptosis in diffuse large B‐cell lymphoma (DLBCL) needs further investigation. The mRNA and protein levels of PAQR3 and low‐density lipoprotein receptor (LDLR) were assessed by qRT‐PCR and WB assays. Cell proliferation was detected by MTT assay and EdU assay. Shrunken mitochondria was counted under transmission electron microscope. Cell ferroptosis was evaluated by measuring the levels of malondialdehyde, reactive oxygen species, glutathione, Fe2+, and the protein expression of ferroptosis‐related markers. PAQR3 and LDLR interaction was confirmed by RIP assay and pull‐down assay. Our study showed that PAQR3 was underexpressed, while LDLR was overexpressed in DLBCL tissues and cells. Functionally, PAQR3 overexpression or LDLR knockdown restrained DLBCL cell proliferation and enhanced ferroptosis. Mechanistically, PAQR3 reduced LDLR expression by inhibiting its mRNA stability. Meanwhile, LDLR overexpression reversed PAQR3‐mediated the promoting on DLBCL cell ferroptosis, and LY294002 (PI3K/AKT inhibitor) eliminated the inhibiting effects of LDLR overexpression on DLBCL cell ferroptosis. Additionally, excessive PAQR3 reduced DLBCL tumor growth by enhancing tumor cell ferroptosis through LDLR‐mediated PI3K/AKT pathway. In conclusion, our data suggested that PAQR3 restrained DLBCL progression by aggravating ferroptosis, which was achieved by inhibiting LDLR expression to repress PI3K/AKT pathway.

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Section: Discussionsupporting

confidence: 92%

Section: Paqr3 Inhibited Dlbcl Tumor Growth Via Promoting Ferroptosis...mentioning

confidence: 99%

“…9 Importantly, LDLR was found to be upregulated in lymphoma cells. 10 However, the role of LDLR in DLBCL progression remains unclear.…”

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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PAQR3 facilitates the ferroptosis of diffuse large B‐cell lymphoma via the regulation of LDLR‐mediated PI3K/AKT pathway

Song,

Zhang,

et al. 2023

Hematological Oncology

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“…The indispensability of lipid metabolism in the cellular physiology of T-cell cancer makes them targetable for therapeutic intervention. Various approaches have shown promising success both in preclinical and clinical settings ( 28 , 29 ). Lipogenic, as well as oxidative metabolism of lipids, has been targeted in T-cell cancer ( 22 , 30 ).…”

Section: Introductionmentioning

confidence: 99%

Orchestral role of lipid metabolic reprogramming in T-cell malignancy

Mehta

Ratre

Soni³

et al. 2023

Front. Oncol.

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The immune function of normal T cells partially depends on the maneuvering of lipid metabolism through various stages and subsets. Interestingly, T-cell malignancies also reprogram their lipid metabolism to fulfill bioenergetic demand for rapid division. The rewiring of lipid metabolism in T-cell malignancies not only provides survival benefits but also contributes to their stemness, invasion, metastasis, and angiogenesis. Owing to distinctive lipid metabolic programming in T-cell cancer, quantitative, qualitative, and spatial enrichment of specific lipid molecules occur. The formation of lipid rafts rich in cholesterol confers physical strength and sustains survival signals. The accumulation of lipids through de novo synthesis and uptake of free lipids contribute to the bioenergetic reserve required for robust demand during migration and metastasis. Lipid storage in cells leads to the formation of specialized structures known as lipid droplets. The inimitable changes in fatty acid synthesis (FAS) and fatty acid oxidation (FAO) are in dynamic balance in T-cell malignancies. FAO fuels the molecular pumps causing chemoresistance, while FAS offers structural and signaling lipids for rapid division. Lipid metabolism in T-cell cancer provides molecules having immunosuppressive abilities. Moreover, the distinctive composition of membrane lipids has implications for immune evasion by malignant cells of T-cell origin. Lipid droplets and lipid rafts are contributors to maintaining hallmarks of cancer in malignancies of T cells. In preclinical settings, molecular targeting of lipid metabolism in T-cell cancer potentiates the antitumor immunity and chemotherapeutic response. Thus, the direct and adjunct benefit of lipid metabolic targeting is expected to improve the clinical management of T-cell malignancies.

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Pathological and imaging features, treatment, and prognosis of primary intraventricular lymphoma: A review of cases from a single center

Wang,

Cui,

Raza

et al. 2024

Heliyon

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Cholesterol metabolism and lipid droplet vacuoles; a potential target for the therapy of aggressive lymphoma

Cited by 6 publications

References 26 publications

PAQR3 facilitates the ferroptosis of diffuse large B‐cell lymphoma via the regulation of LDLR‐mediated PI3K/AKT pathway

PAQR3 facilitates the ferroptosis of diffuse large B‐cell lymphoma via the regulation of LDLR‐mediated PI3K/AKT pathway

Orchestral role of lipid metabolic reprogramming in T-cell malignancy

Pathological and imaging features, treatment, and prognosis of primary intraventricular lymphoma: A review of cases from a single center

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