Syndecan-1 Promotes Hepatocyte-Like Differentiation of Hepatoma Cells Targeting Ets-1 and AP-1

Hollósi, Péter; Váncza, Lóránd; Karászi, Katalin; Dobos, Katalin; Péterfia, Bálint; Tátrai, Erika; Tátrai, Péter; Szarvas, Tibor; Paku, Sándor; Szilák, László; Kovalszky, Ilona

doi:10.3390/biom10101356

Cited by 7 publications

(6 citation statements)

References 101 publications

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“…Their amounts can increase or decrease, while they can also be regulated by glycosylation or sulfation [ 74 ]. Our previous results confirmed that the differentiation of hepatoma cell lines after syndecan-1 transfection acted together with the changes of an HS pattern to a more sulfated one, as indicated by HS-specific antibodies, capable of interfering with the promoter activation of AP1 and Ets1 [ 16 , 75 ]. Such complexity of regulation may account, at least in part, for their often-contradictory behavior.…”

Section: Discussionsupporting

confidence: 79%

“…Our previous experiments indicated that SDC1, the major proteoglycan of the liver, is capable of inducing hepatocyte-like differentiation of hepatoma cell lines [ 16 ], and HS chains in the healthy human liver can interfere with DNA-binding transcription factors [ 23 ]. Together, these results suggested that the regulatory functions of SDC1 in the liver may be far more extensive than previously thought.…”

Section: Discussionmentioning

confidence: 99%

“…The processes of fibrogenesis and hepatocarcinogenesis run concomitantly in cirrhosis-associated HCC; therefore, the overexpression of SDC1 may be more related to cirrhosis than to carcinogenesis, and high expression of SDC1 may ultimately counter rather than support tumor growth. Consistent with this notion, overexpression of full-length or extracellular domain-truncated syndecan-1 in human hepatoma cell lines resulted in cell differentiation via downregulation of the transcription factors Ets-1 and AP-1 [ 16 ].…”

Section: Introductionmentioning

confidence: 87%

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Overexpression of Human Syndecan-1 Protects against the Diethylnitrosamine-Induced Hepatocarcinogenesis in Mice

Reszegi

Karászi

Tóth

et al. 2021

Cancers

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Although syndecan-1 (SDC1) is known to be dysregulated in various cancer types, its implication in tumorigenesis is poorly understood. Its effect may be detrimental or protective depending on the type of cancer. Our previous data suggest that SDC1 is protective against hepatocarcinogenesis. To further verify this notion, human SDC1 transgenic (hSDC1+/+) mice were generated that expressed hSDC1 specifically in the liver under the control of the albumin promoter. Hepatocarcinogenesis was induced by a single dose of diethylnitrosamine (DEN) at an age of 15 days after birth, which resulted in tumors without cirrhosis in wild-type and hSDC1+/+ mice. At the experimental endpoint, livers were examined macroscopically and histologically, as well as by immunohistochemistry, Western blot, receptor tyrosine kinase array, phosphoprotein array, and proteomic analysis. Liver-specific overexpression of hSDC1 resulted in an approximately six month delay in tumor formation via the promotion of SDC1 shedding, downregulation of lipid metabolism, inhibition of the mTOR and the β-catenin pathways, and activation of the Foxo1 and p53 transcription factors that lead to the upregulation of the cell cycle inhibitors p21 and p27. Furthermore, both of them are implicated in the regulation of intermediary metabolism. Proteomic analysis showed enhanced lipid metabolism, activation of motor proteins, and loss of mitochondrial electron transport proteins as promoters of cancer in wild-type tumors, inhibited in the hSDC1+/+ livers. These complex mechanisms mimic the characteristics of nonalcoholic steatohepatitis (NASH) induced human liver cancer successfully delayed by syndecan-1.

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Section: Discussionsupporting

confidence: 79%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 87%

See 1 more Smart Citation

Overexpression of Human Syndecan-1 Protects against the Diethylnitrosamine-Induced Hepatocarcinogenesis in Mice

Reszegi

Karászi

Tóth

et al. 2021

Cancers

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“…Normal, non-cancerous hepatocytes are characterized by the presence of syndecan, which silences MAPK signalling (TLN1, SPTAN1). 107 To summarize, it should be stated that the nfND did not unambiguously affect the behaviour of HepG2 cells, on the one hand, its pro-tumour potential can be presumed; however, strong activation of oxidative phosphorylation and reduced migration of these cells may indicate the continuation of research with some modifications to the nfND.…”

Section: Dovepressmentioning

confidence: 91%

Diamond Nanofilm Normalizes Proliferation and Metabolism in Liver Cancer Cells

Sosnowska¹,

Kutwin²,

Strojny³

et al. 2021

NSA

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Surgical resection of hepatocellular carcinoma can be associated with recurrence resulting from the degeneration of residual volume of the liver. The objective was to assess the possibility of using a biocompatible nanofilm, made of a colloid of diamond nanoparticles (nfND), to fill the side after tumour resection and optimize its contact with proliferating liver cells, minimizing their cancerous transformation. Methods: HepG2 and C3A liver cancer cells and HS-5 non-cancer cells were used. An aqueous colloid of diamond nanoparticles, which covered the cell culture plate, was used to create the nanofilm. The roughness of the resulting nanofilm was measured by atomic force microscopy. Mitochondrial activity and cell proliferation were measured by XTT and BrdU assays. Cell morphology and a scratch test were used to evaluate the invasiveness of cells. Flow cytometry determined the number of cells within the cell cycle. Protein expression in was measured by mass spectrometry. Results: The nfND created a surface with increased roughness and exposed oxygen groups compared with a standard plate. All cell lines were prone to settling on the nanofilm, but cancer cells formed more relaxed clusters. The surface compatibility was dependent on the cell type and decreased in the order C3A >HepG2 >HS-5. The invasion was reduced in cancer lines with the greatest effect on the C3A line, reducing proliferation and increasing the G2/M cell population. Among the proteins with altered expression, membrane and nuclear proteins dominated. Conclusion:In vitro studies demonstrated the antiproliferative properties of nfND against C3A liver cancer cells. At the same time, the need to personalize potential therapy was indicated due to the differential protein synthetic responses in C3A vs HepG2 cells. We documented that nfND is a source of signals capable of normalizing the expression of many intracellular proteins involved in the transformation to non-cancerous cells.

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“…However, the exact role and diagnostic significance of SORBS1 in BRCA are not yet clear. Syndecan-1 (SDC1, also known as CD138) is a key regulator of fatty acid synthesis and catalyzes the formation of mono-unsaturated fatty acids (MUFA) from saturated fatty acids (SFA) [87][88][89][90] .SDC1 has been implicated in various cancers, including BRCA [91][92][93][94] . The inactivation of SDC1 can lead to the consumption of unsaturated fatty acids, thereby inhibiting cancer cells 90,95,96 .…”

Section: Prognostic Gene-drug Interaction Network Analysismentioning

confidence: 99%

Development and Validation of a Prognostic Classifier Based on Metabolism-Related Genes for Breast Cancer

Wang

Chi

et al. 2021

Preprint

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Background: Alterations in lipid metabolism have been implicated in the development of many tumors. However, the contribution of different lipid metabolism pathways to Breast invasive carcinoma (BRCA) remains to be fully established. Here, we attempted to ascertain the prognostic value of lipid metabolism-related genes in BRCA. Methods: We obtained RNA expression data and clinical information for BRCA and normal samples from public databases and downloaded a lipid metabolism-related gene set to harvest lipid metabolism-related genes. IPA was applied to identify the potential pathways and functions of DEGs related to lipid metabolism. Subsequently, univariate and multivariate Cox regression analyses were utilized to construct the prognostic gene signature and independent prognostic analyses. Thereafter, the differential expression of the selected marker genes SDC1 and SORBS1 in clinical tissue samples was verified by qRT-PCR, western blotting, and immunohistochemical experiments. Functional enrichment analysis of prognostic genes was achieved by the GO and KEGG databases. Moreover, Kaplan-Meier analysis, ROC curves, clinical immunohistochemistry conditions and follow-up results were employed to assess the prognostic potency. Potential compounds targeting prognostic genes were then screened by CMap database and a prognostic gene-drug interaction network was constructed using Comparative Toxicogenomics Database.Results: IPA demonstrated that the 162 lipid metabolism-related DEGs we obtained were involved in a variety of lipid metabolism and BRCA pathological signatures. Subsequent functional enrichment analysis of candidate prognostic lipid metabolism DEGs also revealed a similar outcome. The prognostic classifier we constructed comprising SDC1 and SORBS1 has a strong prognostic potency that was verified by the clinical conditions and follow-up results, it also can serve as an independent prognostic marker for BRCA. CMap filtered 37 potential compounds against prognostic genes. CTD indicated that the two prognostic genes had 16 drugs in common. Conclusion: Within this study, we identified a novel prognostic classifier based on two lipid metabolism-related genes: SDC1 and SORBS1. This classifier had accurately predicted the prognosis of our follow-up BRCA patients and this result highlighted a new perspective on the metabolic exploration of BRCA. In addition, SDC1 and SORBS1 could serve as a possible new target for the synthesis of BRCA drugs.

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Syndecan-1 Promotes Hepatocyte-Like Differentiation of Hepatoma Cells Targeting Ets-1 and AP-1

Cited by 7 publications

References 101 publications

Overexpression of Human Syndecan-1 Protects against the Diethylnitrosamine-Induced Hepatocarcinogenesis in Mice

Overexpression of Human Syndecan-1 Protects against the Diethylnitrosamine-Induced Hepatocarcinogenesis in Mice

Diamond Nanofilm Normalizes Proliferation and Metabolism in Liver Cancer Cells

Development and Validation of a Prognostic Classifier Based on Metabolism-Related Genes for Breast Cancer

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