Lipophagy-Related Protein Perilipin-3 and Resistance of Prostate Cancer to Radiation Therapy

Lamprou, Ioannis; Kakouratos, Christos; Tsolou, Avgi; Pavlidis, Pavlos; Xanthopoulou, Erasmia; Nanos, Christos; Tsaroucha, Alexandra; Sivridis, Efthimios; Giatromanolaki, Alexandra; Koukourakis, Michael I.

doi:10.1016/j.ijrobp.2022.01.033

Cited by 10 publications

(8 citation statements)

References 35 publications

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“… 15 In vitro and in vivo investigations in prostate cancer cells indicated that depletion of PLIN3 led to decreased cell proliferation and enhanced radiosensitivity. 36 Similarly, in our study, knocking down PLIN3 in GC cells resulted in impaired cell proliferation, migration, and invasion. However, the role of PLIN3 in the therapeutic response of GC cells remains unclear.…”

Section: Discussionsupporting

confidence: 75%

“…In a study of pancreatic cancer, another digestive system tumor, researchers identified 36 upregulated differentially expressed genes, including PLIN3, and 3 downregulated genes through bioinformatics analysis of 179 tumor tissue samples and 171 normal pancreatic tissue samples 15 . In vitro and in vivo investigations in prostate cancer cells indicated that depletion of PLIN3 led to decreased cell proliferation and enhanced radiosensitivity 36 . Similarly, in our study, knocking down PLIN3 in GC cells resulted in impaired cell proliferation, migration, and invasion.…”

Section: Discussionmentioning

confidence: 99%

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Tumor‐derived Prevotella intermedia aggravates gastric cancer by enhancing Perilipin 3 expression

Liang,

Zhou,

Gao

et al. 2024

Cancer Science

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The indigenous microbial milieu within tumorous tissues exerts a pivotal influence on the genesis and advancement of gastric cancer (GC). This investigation scrutinizes the functions and molecular mechanisms attributed to Prevotella intermedia in the malignant evolution of GC. Isolation of P. intermedia from paired GC tissues was undertaken. Quantification of P. intermedia abundance in 102 tissues was accomplished using quantitative real‐time PCR (qRT‐PCR). Assessment of the biological effects of P. intermedia on GC cells was observed using culture medium supernatant. Furthermore, the protein profile of GC cells treated with tumor‐derived P. intermedia was examined through label‐free protein analysis. The functionality of perilipin 3 (PLIN3) was subsequently confirmed using shRNA. Our investigation revealed that the relative abundance of P. intermedia in tumor tissues significantly surpassed that of corresponding healthy tissues. The abundance of P. intermedia exhibited correlations with tumor differentiation (p = 0.006), perineural invasion (p = 0.004), omentum majus invasion (p = 0.040), and the survival duration of GC patients (p = 0.042). The supernatant derived from tumor‐associated P. intermedia bolstered the proliferation, clone formation, migration, and invasion of GC cells. After indirect co‐cultivation with tumor‐derived P. intermedia, dysregulation of 34 proteins, including PLIN3, was discerned in GC cells. Knockdown of PLIN3 mitigated the malignancy instigated by P. intermedia in GC cells. Our findings posit that P. intermedia from the tumor microenvironment plays a substantial role in the malignant progression of GC via the modulation of PLIN3 expression. Moreover, the relative abundance of P. intermedia might serve as a potential biomarker for the diagnosis and prognosis of GC.

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Section: Discussionsupporting

confidence: 75%

Section: Discussionmentioning

confidence: 99%

Tumor‐derived Prevotella intermedia aggravates gastric cancer by enhancing Perilipin 3 expression

Liang,

Zhou,

Gao

et al. 2024

Cancer Science

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“…Here we have shown for the first time that prostate epithelial cells can mobilize lipids stored in lipid droplets by microlipophagy. Prostate cancer aggressiveness and progression is positively correlated with markers of macrolipophagy, autophagic degradation of lipid droplets, and has been suggested to contribute to treatment resistance thus making our observations on microlipophagy highly interesting for further investigations ( 38 , 81 ). Recent research has shown that mitochondrial metabolism of lipids is regulated by organelle interactions and MAM around mitochondria ( 71 ).…”

Section: Discussionmentioning

confidence: 90%

Ultrastructural analysis of prostate cancer tissue provides insights into androgen-dependent adaptations to membrane contact site establishment

Butler

Evergren

2023

Front. Oncol.

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Membrane trafficking and organelle contact sites are important for regulating cell metabolism and survival; processes often deregulated in cancer. Prostate cancer is the second leading cause of cancer-related death in men in the developed world. While early-stage disease is curable by surgery or radiotherapy there is an unmet need to identify prognostic biomarkers, markers to treatment response and new therapeutic targets in intermediate-late stage disease. This study explored the morphology of organelles and membrane contact sites in tumor tissue from normal, low and intermediate histological grade groups. The morphology of organelles in secretory prostate epithelial cells; including Golgi apparatus, ER, lysosomes; was similar in prostate tissue samples across a range of Gleason scores. Mitochondrial morphology was not dramatically altered, but the number of membrane contacts with the ER notably increased with disease progression. A three-fold increase of tight mitochondria-ER membrane contact sites was observed in the intermediate Gleason score group compared to normal tissue. To investigate whether these changes were concurrent with an increased androgen signaling in the tissue, we investigated whether an anti-androgen used in the clinic to treat advanced prostate cancer (enzalutamide) could reverse the phenotype. Patient-derived explant tissues with an intermediate Gleason score were cultured ex vivo in the presence or absence of enzalutamide and the number of ER-mitochondria contacts were quantified for each matched pair of tissues. Enzalutamide treated tissue showed a significant reduction in the number and length of mitochondria-ER contact sites, suggesting a novel androgen-dependent regulation of these membrane contact sites. This study provides evidence for the first time that prostate epithelial cells undergo adaptations in membrane contact sites between mitochondria and the ER during prostate cancer progression. These adaptations are androgen-dependent and provide evidence for a novel hormone-regulated mechanism that support establishment and extension of MAMs. Future studies will determine whether these changes are required to maintain pro-proliferative signaling and metabolic changes that support prostate cancer cell viability.

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“…The effect of Ori on LPS activity was measured by using the LAL test (Rat Lipopolysaccharides ELISA Kit, CSB-E14247r, CUSABIO, Wuhan, China) (Lamprou et al, 2022). Briefly, a series of concentrations of the Ori (5, 10, 20, and 40 μmol/L) were incubated with LPS (1 μg/mL) for 30 min at 37 C. The absorbance was measured at 450 nm after the addition of 100 μl of the chromogenic substrate.…”

Section: Limulus Amebocyte Lysate (Lal) Testmentioning

confidence: 99%

Oridonin relieves depressive‐like behaviors by inhibiting neuroinflammation and autophagy impairment in rats subjected to chronic unpredictable mild stress

Liang

Wang

et al. 2022

Phytotherapy Research

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Major depressive disorder (MDD) is a severe life‐threatening disorder with increasing prevalence. However, the mechanistic interplay between depression, neuroinflammation, and autophagy is yet to be demonstrated. This study investigated the effect of Oridonin on CUMS‐induced depression, neuroinflammation, and autophagy impairment. Male 4‐week‐old Sprague–Dawley rats were subjected to chronic unpredictable mild stress (CUMS), some of which were injected with Oridonin, fluoxetine (FLX), or their combination at different durations of CUMS. CUMS significantly increased the levels of cytokines (IL‐1β, IL‐18, and caspase‐1), reduced autophagy‐related protein levels (Beclin‐1, p62, Atg5, and LC3B), and caused microglia cells activation. Oridonin prevented and reversed the depressive‐like behavior. Furthermore, it has a stronger and longer‐lasting antidepressant effect than FLX. And the antidepressant effect of Oridonin in combination with fluoxetine was greater than that of high‐dose fluoxetine alone. In addition, Oridonin significantly normalized autophagy‐related protein levels, and reduced levels of cytokines by blocking the interaction between NLRP3 and NEK7. Similarly, Oridonin abolished levels of cytokines and reversed autophagy impairment in LPS‐activated BV2 cells. All these results supported our hypothesis that Oridonin possesses potent anti‐depressive action, which might be mediated via inhibition of neuroinflammation and autophagy impairment by blocking the interaction between NLRP3 and NEK7.

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Lipophagy-Related Protein Perilipin-3 and Resistance of Prostate Cancer to Radiation Therapy

Cited by 10 publications

References 35 publications

Tumor‐derived Prevotella intermedia aggravates gastric cancer by enhancing Perilipin 3 expression

Tumor‐derived Prevotella intermedia aggravates gastric cancer by enhancing Perilipin 3 expression

Ultrastructural analysis of prostate cancer tissue provides insights into androgen-dependent adaptations to membrane contact site establishment

Oridonin relieves depressive‐like behaviors by inhibiting neuroinflammation and autophagy impairment in rats subjected to chronic unpredictable mild stress

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