Lipid rafts disruption induces apoptosis by attenuating expression of LRP6 and survivin in triple negative breast cancer

Badana, Anil Kumar; Chintala, Madhuri; Gavara, Murali Mohan; Naik, Shailender; Kumari, Seema; Kappala, Vijaya Rachel; Iska, Bhaskar Reddy; Malla, Rama Rao

doi:10.1016/j.biopha.2017.10.045

Cited by 43 publications

(34 citation statements)

References 55 publications

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“…Survivin expression has been reported in many types of cancer, and high expression often indicates a more aggressive and poor prognosis of the tumor. Studies by Badana et al showed that in triple-negative breast cancer, the destruction of lipid rafts induces the apoptosis of tumor cells by attenuating the expression of survivin and LRP6 [ 33 ]. Therefore, survivin is not only a good diagnostic factor but also a good prognostic factor, and it also plays an important role in TNBC antitumor therapy.…”

Section: Discussionmentioning

confidence: 99%

Coexpression Network Analysis of Genes Related to the Characteristics of Tumor Stemness in Triple-Negative Breast Cancer

Suo

Zuo

Zhang

et al. 2020

BioMed Research International

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Cancer stem cells (CSCs) are subsets of cells with the ability of self-renewal and differentiation in neoplasm, which are considered to be related to tumor heterogeneity. It has been reported that CSCs act on tumorigenesis and tumor biology of triple-negative breast cancer (TNBC). However, the key genes that cause TNBC showing stem cell characteristics are still unclear. We combined the RNA sequencing (RNA-seq) data from The Cancer Genome Atlas (TCGA) database and mRNA expression-based stemness index (mRNAsi) to further analyze mRNAsi with regard to molecular subtypes, tumor depth, and pathological staging characteristics of breast cancer (BC). Secondly, we extract the differential gene expression of tumor vs. normal group and TNBC vs. other subtypes of BC group, respectively, and intersect them to achieve precise results. We used a weighted gene coexpression network analysis (WGCNA) to screen significant gene modules and the functions of selected genes including BIRC5, CDC25A, KIF18B, KIF2C, ORC1, RAD54L, and TPX2 were carried out through gene ontology (GO) functional annotation. The Oncomine, bc-GenExMiner v4.4, GeneMANIA, Kaplan-Meier Plotter (KM-plotter), and GEPIA were used to verify the expression level and functions of key genes. In this study, we found that TNBC had the highest stem cell characteristics in BC compared with other subtypes. The lower the mRNAsi score, the better the overall survival and treatment outcome. Seven key genes of TNBC were screened and functional annotation indicated that there were strong correlations between them, relating to nuclear division, organelle fission, mitotic nuclear division, and other events that determine cell fate. Among these genes, we found four genes that were highly associated with adverse survival events. Seven key genes identified in this study were found to be closely related to the maintenance of TNBC stemness, and the overexpression of four showed earlier recurrence. The overall survival (OS) curves of all key genes between differential expression level crossed at around nine-year follow-up, which was consistent with the trend of the OS curve related to mRNAsi. These findings may provide new ideas for screening therapeutic targets in order to depress TNBC stemness.

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Section: Discussionmentioning

confidence: 99%

Coexpression Network Analysis of Genes Related to the Characteristics of Tumor Stemness in Triple-Negative Breast Cancer

Suo

Zuo

Zhang

et al. 2020

BioMed Research International

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“…Very recently, disruption of lipid rafts on breast cancer (BC) cell lines MDA-MB231 and MDA-MB468, using the cholesterol depleting agent methyl-β-cyclodextrin, resulted in reduced proliferation and migration, induction of apoptosis evidenced by cell shrinkage, membrane blebbing, nuclear condensation, and chromatin cleavage (47). It was already demonstrated for BC, that lipid rafts disruption causes decreased migration and invasion downregulating caveolin-1 along with urokinase-type plasminogen activator receptor (uPAR) and matrix metallopeptidase 9 (MMP-9) (48).…”

Section: Cholesterol As Signal Molecule On Membrane Raftsmentioning

confidence: 99%

Cholesterol and Its Metabolites in Tumor Growth: Therapeutic Potential of Statins in Cancer Treatment

et al. 2019

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Cholesterol is essential for cell function and viability. It is a component of the plasma membrane and lipid rafts and is a precursor for bile acids, steroid hormones, and Vitamin D. As a ligand for estrogen-related receptor alpha (ESRRA), cholesterol becomes a signaling molecule. Furthermore, cholesterol-derived oxysterols activate liver X receptors (LXRs) or estrogen receptors (ERs). Several studies performed in cancer cells reveal that cholesterol synthesis is enhanced compared to normal cells. Additionally, high serum cholesterol levels are associated with increased risk for many cancers, but thus far, clinical trials with 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (statins) have had mixed results. Statins inhibit cholesterol synthesis within cells through the inhibition of HMG-CoA reductase, the rate-limiting enzyme in the mevalonate and cholesterol synthetic pathway. Many downstream products of mevalonate have a role in cell proliferation, since they are required for maintenance of membrane integrity; signaling, as some proteins to be active must undergo prenylation; protein synthesis, as isopentenyladenine is an essential substrate for the modification of certain tRNAs; and cell-cycle progression. In this review starting from recent acquired findings on the role that cholesterol and its metabolites fulfill in the contest of cancer cells, we discuss the results of studies focused to investigate the use of statins in order to prevent cancer growth and metastasis.

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“…26 Cancer cells alter antioxidant defense system against the elevated levels of ROS to overcome the stress of reactive metabolite. 27 TNBC shows lower levels of glutathione compared with normal cells, thus sensitive to inhibitors of glutathione biosynthesis that was rescued by N-acetylcysteine, demonstrating a dependence on glutathione production to suppress ROS and support tumor cell survival. Moreover, high levels of γ-glutamylcysteine ligase, the rate-limiting enzyme in glutathione biosynthesis, had significantly poorer survival.…”

Section: Cancer and Metabolomic Profilingmentioning

confidence: 99%

“…Elevated expression of ROS is associated with cancers due deregulated metabolic activity, loss of mitochondria and peroxisome activity, activation of an oncogene, and increased expression of oxidases, cyclooxygenases, lipoxygenases, and thymidine phosphorylase . Cancer cells alter antioxidant defense system against the elevated levels of ROS to overcome the stress of reactive metabolite . TNBC shows lower levels of glutathione compared with normal cells, thus sensitive to inhibitors of glutathione biosynthesis that was rescued by N‐acetylcysteine, demonstrating a dependence on glutathione production to suppress ROS and support tumor cell survival.…”

Section: Introductionmentioning

confidence: 99%

Recent advances in metabolomics of triple negative breast cancer

Kumari

Malla

2020

Breast J

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Triple‐negative Breast Cancer (TNBC) is considered as the most aggressive subtype of breast cancer. Metabolic profiling has a great significance in cancer research due to profound changes in the metabolism of cancer cells. It has been used to investigate the entire set of metabolites and changes associated with it in disease conditions. These changes in the expression levels of metabolites bring functional changes associated with the pharmacological or nutritional intervention. The present minireview presents a brief note on changes associated with TNBC aggressiveness in terms of metabolomics.

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Lipid rafts disruption induces apoptosis by attenuating expression of LRP6 and survivin in triple negative breast cancer

Cited by 43 publications

References 55 publications

Coexpression Network Analysis of Genes Related to the Characteristics of Tumor Stemness in Triple-Negative Breast Cancer

Coexpression Network Analysis of Genes Related to the Characteristics of Tumor Stemness in Triple-Negative Breast Cancer

Cholesterol and Its Metabolites in Tumor Growth: Therapeutic Potential of Statins in Cancer Treatment

Recent advances in metabolomics of triple negative breast cancer

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