Identification of CETP as a molecular target for estrogen positive breast cancer cell death by cholesterol depleting agents

Esau, Luke; Sagar, Sunil; Bangarusamy, Dhinoth Kumar; Kaur, Mandeep

doi:10.18632/genesandcancer.122

Cited by 24 publications

(25 citation statements)

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“…On the other hand, at the 24‐hr time‐point, many genes were consistently upregulated in at least four cell lines. Table 1 displays the list of these genes, the information on family, molecular function ligands (lipid transport‐associated), subcellular localization, and cancer‐associated expression patterns of their encoded proteins are also provided (Carrara et al., 2018; Chen et al., 2020; Esau et al., 2016; Gordon et al., 2019; D. Jiang et al., 2020; Koochekpour et al., 2007; Swanton et al., 2007; Thorsen et al., 2011; Verma et al., 2020; Yang, He, et al., 2019; M. Zhang, Xiang, et al., 2020; Zheng et al., 2018). It was observed that STARD4, OSBPL9 LDLR, and SCARB1 genes were significantly upregulated in all the LPDS‐treated (24 hr) cell lines, whereas CERT1, OSBPL5, OSBPL1A, APOLD1, APOL5, CTEP, PSAP, CFHR4, APOO, and SLC27A6 were upregulated in at least four of the five cell lines (Table 1 and Figure 2).…”

Section: Resultsmentioning

confidence: 99%

“…On the other hand, at the 24-hr time-point, many genes were consistently upregulated in at least four cell lines. Table 1 displays the list of these genes, the information on family, molecular function ligands (lipid transport-associated), subcellular localization, and cancer-associated expression patterns of their encoded proteins are also provided (Carrara et al, 2018;Chen et al, 2020;Esau et al, 2016;Gordon et al, 2019;D. Jiang et al, 2020;Koochekpour et al, 2007;Swanton et al, 2007;Thorsen et al, 2011;Verma et al, 2020;Yang, He, et al, 2019;M.…”

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Expression of lipid transport‐associated genes in lipid‐deprived cancer cells

et al. 2021

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Genes to Cells | INTRODUCTIONCancer cells are known to modulate their de novo lipid synthesis pathway in response to changes in extracellular lipid availability (Daniëls et al., 2014;Munir et al., 2019). It has been observed that the expression of genes involved in de novo lipid synthesis is differentially modulated in cancer cells under low-lipid environment (Daniëls et al., 2014). We have recently shown that under lipid-deprived environment, the lipidomic profiles of cancer cells are largely altered (Munir et al., 2019). Moreover, cellular lipid load is also significantly reduced under such conditions (Munir et al., 2019). Multiple works have studied the modulation of de novo lipid synthesis in metabolically stressed cancer cells (Munir et al., 2019); however, genes associated with lipid transport are not widely investigated in this regard. Cellular lipid homeostasis is immensely altered under lipiddeprived conditions, and there is possibility that lipid transport proteins (LTPs) also play a role in this phenomenon. Lipids are distributed to different cellular membranes via vesicular or nonvesicular cellular lipid trafficking processes (Levine, 2004).Nonvesicular transport-that constitutes the bulk of lipid traffic-is mediated by LTPs, which transfer a small number of lipids at the same time using hydrophobic cavities that stabilize lipid molecules outside membranes (Wong et al., 2019). In addition, many species of LTPs function as second messengers in key signaling pathways that control cell survival, proliferation, and migration. Previous works have implicated LTPs in cancer-associated signal transduction cascades. Recent works suggest that LTPs play an important role in cancer progression and metastasis (reviewed in (Peretti et al., 2019)). The aim of the presented work was to study the expression of LTP genes under lipid-reduced environment and to identify the common genes that are up-or down-regulated under such conditions in a panel of biologically diverse cancer cell lines. | RESULTS AND DISCUSSIONFor the presented work we selected a biologically diverse panel of cancer cell lines -two prostate cancer cell lines

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Expression of lipid transport‐associated genes in lipid‐deprived cancer cells

et al. 2021

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Mining the plasma-proteome associated genes in patients with gastro-esophageal cancers for biomarker discovery

Vizeacoumar

Guo

Dwernychuk

et al. 2021

Sci Rep

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Gastro-esophageal (GE) cancers are one of the major causes of cancer-related death in the world. There is a need for novel biomarkers in the management of GE cancers, to yield predictive response to the available therapies. Our study aims to identify leading genes that are differentially regulated in patients with these cancers. We explored the expression data for those genes whose protein products can be detected in the plasma using the Cancer Genome Atlas to identify leading genes that are differentially regulated in patients with GE cancers. Our work predicted several candidates as potential biomarkers for distinct stages of GE cancers, including previously identified CST1, INHBA, STMN1, whose expression correlated with cancer recurrence, or resistance to adjuvant therapies or surgery. To define the predictive accuracy of these genes as possible biomarkers, we constructed a co-expression network and performed complex network analysis to measure the importance of the genes in terms of a ratio of closeness centrality (RCC). Furthermore, to measure the significance of these differentially regulated genes, we constructed an SVM classifier using machine learning approach and verified these genes by using receiver operator characteristic (ROC) curve as an evaluation metric. The area under the curve measure was > 0.9 for both the overexpressed and downregulated genes suggesting the potential use and reliability of these candidates as biomarkers. In summary, we identified leading differentially expressed genes in GE cancers that can be detected in the plasma proteome. These genes have potential to become diagnostic and therapeutic biomarkers for early detection of cancer, recurrence following surgery and for development of targeted treatment.

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“…The stage-related expression of these genes suggests their potential role in the disease progression and utility as monitoring markers or therapeutic targets. The cholesteryl ester transfer protein (CETP) for example maintains cholesterol homeostasis and has been identi ed as a potential target for estrogen positive breast cancer (54). Conversely, AHNAK can act as a tumour suppressor gene and mediates the negative regulation of cell growth (55) While our work provides a signi cant amount of novel information regarding the behavior of cancerrelated molecules in esophagus and stomach tumors, it does not assess the level of gene expression based on the molecular classi cation of stomach and esophageal cancers (7).…”

Section: Discussionmentioning

confidence: 99%

Characterization of Leading Dysregulated Plasma-Proteome Associated Genes in Patients with Gastro-Esophageal Cancers.

Vizeacoumar¹,

Dwernychuk²,

Zaidi³

et al. 2020

Preprint

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Background: Gastro-esophageal cancers are one of the major causes of cancer-related death in the world. There is a need for novel biomarkers in the management of gastro-esophageal cancers to identify new therapeutic targets and to yield predictive response to the available therapies. Our study aims to identify leading genes that are dysregulated (upregulated or downregulated) in patients with gastro-esophageal cancers.Methods: We examined gene expression data for those genes whose protein products can be detected in the plasma in 600 independent tumor samples and 46 matching normal tissue samples using the Cancer Genome Atlas (TCGA) to identify leading genes that are dysregulated in patients with gastro-esophageal cancers. Non-parametric Mann-Whitney-U test was used to evaluate differential expression of genes using a cut-off of P< 0.05.Results: The comparison between tumors sample and healthy tissue showed BIRC5 (p=2.61 E-08), APOC2 (p=3.23E-08), CENPF (p=4.38E-08), STMN1 (p=5.74E-08), and HNRPC (p=8.21E-08) were the leading genes significantly overexpressed in esophageal cancer whereas CST1 (p=3.97 E-21), INHBA (p=9.22E-20), ACAN (p=1.08E-19), HSP90AB1 (p=2.62E-19), and HSPD1 (p=3.91E-19) were the leading genes that were overexpressed in stomach cancer. Conversely, C16orf89 (9.78E-08), AR (1.01E-07), CKB (1.17E-07), ADH1B (1.79E-07), and NCAM1 (2.15E-07) were the leading gene that were significantly downregulated in esophageal cancer whereas GPX3 (1.65E-19), CLEC3B (5.70E-19), CFD (5.68E-18), GSN (4.5IE-17), and CCL14 (1.12E-16) were significantly downregulated in stomach cancer. Furthermore, Stage-based examination showed stage-specific differential expression of various genes as well as stage-wise increasing or decreasing up-regulation or down-regulation of selected genes, respectively. Conclusions: The present study identified leading upregulated and downregulated genes in gastro-esophageal cancers that can be detected in the plasma proteome. These genes have potential to become diagnostic and therapeutic biomarkers for early detection of cancer, recurrence following surgery and for development of targeted-treatment.

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Identification of CETP as a molecular target for estrogen positive breast cancer cell death by cholesterol depleting agents

Cited by 24 publications

References 47 publications

Expression of lipid transport‐associated genes in lipid‐deprived cancer cells

Expression of lipid transport‐associated genes in lipid‐deprived cancer cells

Mining the plasma-proteome associated genes in patients with gastro-esophageal cancers for biomarker discovery

Characterization of Leading Dysregulated Plasma-Proteome Associated Genes in Patients with Gastro-Esophageal Cancers.

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