Cell fusion enhances energy metabolism of mesenchymal tumor hybrid cells to sustain their proliferation and invasion
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ABSTRACT:
PROVIDER: PRJNA719777 | ENA |
REPOSITORIES: ENA
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Project description:Cell-to-cell fusion is emerging as a key element of the metastatic process in various cancer types. We recently showed that hybrids made from the spontaneous merging of pre-malignant (IMR90 E6E7, i.e. E6E7) and malignant (IMR90 E6E7 RST, i.e. RST) mesenchymal cells recapitulate the main features of human undifferentiated pleomorphic sarcoma (UPS), with a highly rearranged genome and increased spreading capacities. To better characterize the intrinsic properties of these hybrids, we investigated here their metabolic energy profile compared to their parents. Our results unveiled that hybrids harbored a Warburg-like metabolism, like their RST counterparts. However, hybrids displayed a much greater metabolic activity, enhancing glycolysis to proliferate. Interestingly, modifying the metabolic environmental conditions through the use of 5-aminoimidazole-4-carbox-amide-1-β-D-ribofuranoside (AICAR), an activator of the 5’-adenosine monophosphate (AMP)-activated protein kinase (AMPK), specifically reduced the growth of hybrids, and also abrogated the invasive capacity of hybrids displaying enhanced glycolysis. Furthermore, AICAR efficiently blocked the tumoral features related to the aggressiveness of human UPS cell lines. Altogether, our findings strongly suggest that hybrids rely on higher energy flux to proliferate and that a drug altering this metabolic equilibrium could impair their survival and be potentially considered as a novel therapeutic strategy.
2021-08-04 | GSE171471 | GEO
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2026-06-11 | E-MTAB-17074 | biostudies-arrayexpress
Project description:Obesity is characterized by abnormal adipose development and disruptive energy metabolism, and with many factors involved. Oxytocin receptor (OXTR) affects social behaviors, mammary gland development and cancers. In this study, transgenic overexpression of OXTR under β-actin promoter (++Oxtr) exhibited a lean phenotype with reduced fat accumulation and without significant change in food consumption. OXTR overexpression enhanced energy expenditure, adaptive thermogenesis and glucose tolerance. Morphologically, OXTR overexpression displayed a browning phenotype in adipose tissue accompanied by higher cell counts and smaller adipocytes. Gene expression analysis revealed elevated levels of Brown Adipose Tissue (BAT) markers, fatty acid transport proteins and glucose transporters in adipose tissues. High OXTR ameliorated high-fat-diet induced obesity with improvement of metabolic parameters. Furthermore, OXTR overexpression led to an activation of PPAR signaling, increased energy consumption, reduced fat accumulation and weight loss. We have identified OXTR to be a critical regulator of energy metabolism and thermogenesis. That OXTR enhances adaptive thermogenesis and energy metabolism may present a novel therapeutic target for metabolic disorders.
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Project description:Human induced pluripotent stem cells (iPS cells) resemble embryonic stem cells and can differentiate into cell derivatives of all three germ layers. However, frequently the differentiation efficiency of iPS cells into some lineages is rather poor. Here, we found that fusion of iPS cells with human hematopoietic stem cells (HSC) enhances iPS cell differentiation. Such iPS hybrids showed a prominent differentiation bias towards hematopoietic lineages but also towards other mesendodermal lineages. Additionally, during differentiation of iPS hybrids expression of early mesendodermal markers - Brachyury (T), MIX1 Homeobox-Like Protein 1 (MIXL1) and Goosecoid (GSC) - appeared with faster kinetics than in parental iPS cells. Following iPS hybrid differentiation there was a prominent induction of NODAL and inhibition of NODAL signaling blunted mesendodermal differentiation. This indicates that NODAL signaling is critically involved in mesendodermal bias of iPS hybrid differentiation. In summary, we demonstrate that iPS cell fusion with HSC prominently enhances iPS differentiation. 11 samples were hybridized GeneChip Human Gene 1.0 ST Arrays (Affymetrix)
2014-08-06 | E-GEOD-58457 | biostudies-arrayexpress
Project description:Background: Lidocaine, a widely used local anesthetic, has been reported to exert anti-cancer activity against hepatocellular carcinoma (HCC). However, its molecular mechanisms remain incompletely understood. This study sought to elucidate the mechanisms underlying lidocaine’s effects on HCC. Methods: Potential lidocaine targets in HepG2 cells were identified using network pharmacology and transcriptomic profiling. The prognostic and clinical relevance of candidate genes were assessed through bioinformatics analyses. Key targets were validated by RT–qPCR. The functional role of SLC6A3 in regulating HepG2 cell proliferation, apoptosis, migration, and invasion was examined through in vitro assays. Results: Network pharmacology predicted 433 lidocaine targets, while transcriptomic profiling revealed 442 differentially expressed genes. Nine overlapping targets (SLC6A3, CHRNB2, GRIN1, ADRA2C, LIPE, SLC18A2, KCNQ2, TERT, and ALOX12) were enriched in pathways associated with neuronal signaling, synaptic transmission, and drug addiction. Among these, SLC6A3 and TERT were significantly associated with poor prognosis and increased tumor immune infiltration. Both genes demonstrated predictive value for 1- to 2-year survival, with SLC6A3 showing the stronger prognostic relevance. Molecular docking revealed hydrophobic interactions between lidocaine and SLC6A3 (binding energy: −5.6 kcal/mol). Silencing of SLC6A3 markedly promoted apoptosis and suppressed proliferation, migration, and invasion of HepG2 cells. Collectively, these findings suggest that lidocaine inhibits HCC progression by targeting and downregulating SLC6A3. Conclusion: Lidocaine exerts anti-HCC effects by directly targeting and downregulating SLC6A3, thereby inducing apoptosis and suppressing tumor progression.
2026-03-31 | GSE325921 | GEO
Project description:Salmonella invasion of non-phagocytic cells is a dynamic process that requires the translocation of effector proteins into host cells by a type III secretion system (T3SS1) encoded on Salmonella pathogenicity island 1 (SPI1). The signals involved in T3SS1 induction in vivo are not known, but SPI1-induced invasive Salmonella can be prepared by growth in synthetic media. Here we compared two different methods of preparing SPI1-induced bacteria by using a combination of transcriptome analysis, a single-cell reporter assay and intracellular gene expression analysis to reveal clear differences between these two bacterial populations that are reflected in their ability to interact with cultured epithelial cells. Invasion efficiency and intracellular replication were greater for bacteria grown with aeration to late-log phase compared to those grown without aeration to stationary phase. No significant differences in SPI1 regulon expression were revealed by transcriptome analysis. By contrast, surface appendage and stress response genes were considerably changed. Single cell analyses of gene expression revealed variation in the frequency of SPI1-induced bacteria and a correlation between SPI1-induction and the presence of flagella. The expression of virulence genes following invasion of cultured epithelial cells was also found to be predetermined by pre-invasion growth conditions. Key words: epithelial, flagella, invasion, motility, Salmonella-containing vacuole, treatment of shaking versus treatment of static growth conditions for St-SL1344
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