Cancer cell lipid class homeostasis is altered under nutrient-deprivation but stable under hypoxia

Lisec, Jan; Jaeger, Carsten; Rashid, Rida; Munir, Rimsha; Zaidi, Nousheen

doi:10.1186/s12885-019-5733-y

Cited by 20 publications

(20 citation statements)

References 36 publications

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“…These data, as well as previous studies demonstrate that there are fundamental differences between the lipidome of cancer and non-cancer cells [ 44 , 56 – 58 ]. Non-cancer cells typically exhibit neutral total membrane charge due to the presence of zwitterionic phospholipids (PC and SM) on the outer leaflet of the membrane and PS and PE located in the inner leaflet of the membrane [ 59 – 61 ].…”

Section: Discussionsupporting

confidence: 86%

Identification of lipidomic profiles associated with drug-resistant prostate cancer cells

et al. 2021

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Background The association of circulating lipids with clinical outcomes of drug-resistant castration-resistant prostate cancer (DR-CRPC) is not fully understood. While it is known that increases in select lipids correlate to decreased survival, neither the mechanisms mediating these alterations nor the correlation of resistance to drug treatments is well characterized. Methods This gap-in-knowledge was addressed using in vitro models of non-cancerous, hormone-sensitive, CRPC and drug-resistant cell lines combined with quantitative LC-ESI-Orbitrap-MS (LC-ESI-MS/MS) lipidomic analysis and subsequent analysis such as Metaboanalyst and Lipid Pathway Enrichment Analysis (LIPEA). Results Several lipid regulatory pathways were identified that are associated with Docetaxel resistance in prostate cancer (PCa). These included those controlling glycerophospholipid metabolism, sphingolipid signaling and ferroptosis. In total, 7460 features were identified as being dysregulated between the cell lines studied, and 21 lipid species were significantly altered in drug-resistant cell lines as compared to nonresistant cell lines. Docetaxel resistance cells (PC3-Rx and DU145-DR) had higher levels of phosphatidylcholine (PC), oxidized lipid species, phosphatidylethanolamine (PE), and sphingomyelin (SM) as compared to parent control cells (PC-3 and DU-145). Alterations were also identified in the levels of phosphatidic acid (PA) and diacylglyceride (DAG), whose levels are regulated by Lipin (LPIN), a phosphatidic acid phosphatase that converts PA to DAG. Data derived from cBioPortal demonstrated a population of PCa patients expressing mutations aligning with amplification of LPIN1, LPIN2 and LPIN3 genes. Lipin amplification in these genes correlated to decreased survival in these patients. Lipin-1 mRNA expression also showed a similar trend in PCa patient data. Lipin-1, but not Lipin-2 or − 3, was detected in several prostate cancer cells, and was increased in 22RV1 and PC-3 cell lines. The increased expression of Lipin-1 in these cells correlated with the level of PA. Conclusion These data identify lipids whose levels may correlate to Docetaxel sensitivity and progression of PCa. The data also suggest a correlation between the expression of Lipin-1 in cells and patients with regards to prostate cancer cell aggressiveness and patient survivability. Ultimately, these data may be useful for identifying markers of lethal and/or metastatic prostate cancer.

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Section: Discussionsupporting

confidence: 86%

Identification of lipidomic profiles associated with drug-resistant prostate cancer cells

et al. 2021

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“…These data, as well as previous studies demonstrates that there are fundamental differences between the lipidome of non-cancer and cancer cells [44,[59][60][61]. Non-cancer cells typically exhibit neutral total membrane charge due to the presence of zwitterionic phospholipids (PC and SM) on the outer leaflet of the membrane and PS and PE located in the inner leaflet of the membrane [62][63][64].…”

Section: Discussionsupporting

confidence: 82%

Identification of Lipidomic Profiles Associated with Drug-Resistant Prostate Cancer Cells

Ingram

Mansoura

Chou³

et al. 2020

Preprint

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BackgroundThe association of circulating lipids with clinical outcomes of drug-resistant castration-resistant prostate cancer (CRPC) is not fully understood. While it is known that increases in select lipids correlates to decreased survival, neither the mechanisms mediating these alterations nor the correlation of resistance to drug treatments are well characterized.MethodsWe addressed this gap-in-knowledge using in vitro models of non-cancerous, hormone-sensitive, CRPC and drug-resistant cell lines combined with quantitative LC-ESI-Orbitrap-MS lipidomic analysis and subsequent analysis such as Metaboanalyst and Lipid Pathway Enrichment (LIPEA).ResultsThis approach identified several lipid regulatory pathways associated with Docetaxel resistance in PCa. These included those controlling glycerophospholipid metabolism, sphingolipid signaling pathways and ferroptosis. In total, 7,460 features were identified as being dysregulated between the cell lines studied, and 21 lipid species were significantly altered in drug-resistant cell lines as compared to nonresistant cell lines. Docetaxel resistance cells (PC3-Rx and DU145-DR) and had higher levels of phosphatidylcholine (PC), oxidized lipid species, phosphatidylethanolamine (PE), and sphingomyelin (SM) as compared to parent control cells (PC-3 and DU-145). These cells also had higher levels of ceramides release into the media.ConclusionThese data identify lipids whose levels may correlate to Docetaxel sensitivity and progression of prostate cancer.

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“…Similarly, cancer lipid profiles showed different findings in the degree of fatty acyl saturation in cancer patients [ 55 , 56 , 57 ]. We report decreased levels of circulatory saturated free fatty acids in the transition from healthy control to CLD and HCC patients that might be due to their role in activation of inflammatory cytokines [ 58 ].…”

Section: Discussionmentioning

confidence: 99%

Remodeling Lipids in the Transition from Chronic Liver Disease to Hepatocellular Carcinoma

Ismail

Elfert

Helal

et al. 2020

Cancers

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Hepatocellular carcinoma (HCC) is a worldwide health problem. HCC patients show a 50% mortality within two years of diagnosis. To better understand the molecular pathogenesis at the level of lipid metabolism, untargeted UPLC MS—QTOF lipidomics data were acquired from resected human HCC tissues and their paired nontumor hepatic tissues (n = 46). Blood samples of the same HCC subjects (n = 23) were compared to chronic liver disease (CLD) (n = 15) and healthy control (n = 15) blood samples. The participants were recruited from the National Liver Institute in Egypt. The lipidomics data yielded 604 identified lipids that were divided into six super classes. Five-hundred and twenty-four blood lipids were found as significantly differentiated (p < 0.05 and qFDR p < 0.1) between the three study groups. In the blood of CLD patients compared to healthy control subjects, almost all lipid classes were significantly upregulated. In CLD patients, triacylglycerides were found as the most significantly upregulated lipid class at qFDR p = 1.3 × 10−56, followed by phosphatidylcholines at qFDR p = 3.3 × 10−51 and plasmalogens at qFDR p = 1.8 × 10-46. In contrast, almost all blood lipids were significantly downregulated in HCC patients compared to CLD patients, and in HCC tissues compared to nontumor hepatic tissues. Ceramides were found as the most significant lipid class (qFDR p = 1 × 10−14) followed by phosphatidylglycerols (qFDR p = 3 × 10−9), phosphatidylcholines and plasmalogens. Despite these major differences, there were also common trends in the transitions between healthy controls, CLD and HCC patients. In blood, several mostly saturated triacylglycerides showed a continued increase in the trajectory towards HCC, accompanied by reduced levels of saturated free fatty acids and saturated lysophospatidylcholines. In contrast, the largest overlaps of lipid alterations that were found in both HCC tissue and blood comparisons were decreased levels of phosphatidylglycerols and sphingolipids. This study highlights the specific impact of HCC tumors on the circulating lipids. Such data may be used to target lipid metabolism for prevention, early detection and treatment of HCC in the background of viral-related CLD etiology.

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Cancer cell lipid class homeostasis is altered under nutrient-deprivation but stable under hypoxia

Cited by 20 publications

References 36 publications

Identification of lipidomic profiles associated with drug-resistant prostate cancer cells

Identification of lipidomic profiles associated with drug-resistant prostate cancer cells

Identification of Lipidomic Profiles Associated with Drug-Resistant Prostate Cancer Cells

Remodeling Lipids in the Transition from Chronic Liver Disease to Hepatocellular Carcinoma

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