Downregulation of hepatoma-derived growth factor suppresses the malignant phenotype of U87 human glioma cells

Zhang, Aixia; Long, Weiguo; Guo, Zhendong; Guo, Zhang; Cao, Brian

doi:10.3892/or.2012.1768

Cited by 7 publications

(4 citation statements)

References 28 publications

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“…As is well known, lentiviruses have the capacity to integrate into the genome of host cells; thus, they are extensively used as vectors for shRNA expression 28. Some studies showed that HDGF depletion significantly reduced cancer cell proliferation, migration and invasion, including in gallbladder cancer, gastric cancer, and human glioma cells,29–31 but in contrast to the above results, Guo, Z., et al found that downregulation of HDGF stimulated cell migration and invasion in breast cancer 32. We first investigated the correlations between HDGF expression and BCa, and we found that HDGF deletion significantly inhibited the malignant phenotype of T24 and 253J cells, including proliferation, colony formation, migration and invasion.…”

Section: Discussionmentioning

confidence: 99%

<p>Downregulation of HDGF inhibits the tumorigenesis of bladder cancer cells by inactivating the PI3K-AKT signaling pathway</p>

Zhang¹,

Chang²,

Chen³

et al. 2019

CMAR

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BackgroundHepatoma-derived growth factor (HDGF) is a heparin-binding protein that has been observed to be abnormally expressed in numerous malignancies, but the definite role of HDGF in bladder cancer (BCa) has not been clarified. Here, we conduct the present study to evaluate correlations between HDGF and BCa.MethodsBioinformatics analysis was used to evaluate HDGF expression levels in BCa tissues. The effect of HDGF on cell proliferation, migration, invasion, cell cycle and apoptosis was analyzed utilizing CCK-8, clone formation, Transwell assays and flow cytometry, respectively. In addition, the xenograft tumor model was established.ResultsBased on bioinformatics analysis, we noticed that HDGF was highly expressed in BCa tissues and was positively correlated with poor prognosis in patients. Knockdown of HDGF markedly reduced tumorigenesis in BCa cells. Furthermore, the results of flow cytometry showed that HDGF deletion enhanced apoptosis in T24 and 253J cells and led to cell cycle arrest in G1 phase. In further studies, we found that tumor growth was inhibited in xenograft nude mouse models with HDGF deletion. The results of RNA-seq analysis revealed that the PI3K-AKT signaling pathway-related genes were obviously changed in HDGF-deficient 253J cells, and this result was further confirmed by Western blot analysis.ConclusionIn summary, we suggest that HDGF plays a substantial role in BCa and promotes tumor development and progression by regulating the PI3K-AKT signaling pathway, which provides a promising target for BCa treatment.

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Section: Discussionmentioning

confidence: 99%

<p>Downregulation of HDGF inhibits the tumorigenesis of bladder cancer cells by inactivating the PI3K-AKT signaling pathway</p>

Zhang¹,

Chang²,

Chen³

et al. 2019

CMAR

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“…Besides, ionizing radiation enhances esophageal epithelial cell migration and invasion through a paracrine mechanism involving stromal-derived HGF [20]. HGF contributed to the HDGF-associated aggressive behavior of cancer cells [32]. Our study also showed that irradiated fibroblasts promoted ESCC cells scattering abilities, which was a well-characterized behavior activated by HGF/c-Met system [16].…”

Section: Discussionmentioning

confidence: 77%

Irradiated fibroblasts promote epithelial–mesenchymal transition and HDGF expression of esophageal squamous cell carcinoma

Bao

Wang

et al. 2015

Biochemical and Biophysical Research Communications

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“…Signaling through receptor tyrosine kinases such as hepatocyte growth factor and epidermal growth factor receptor are known to drive the malignant behaviors of U87MG cells, at least in part, via downstream Akt signaling. 4,36,37 We previously showed that RNAi-mediated knockdown of ACSVL3 disrupted RTK-Akt signaling. 4 Lipid raftsplasma membrane microdomains that are enriched in sphingolipids and cholesterolare thought to be organizing centers or platforms for signaling receptors.…”

Section: Discussionmentioning

confidence: 99%

Very long-chain acyl-CoA synthetase 3 mediates onco-sphingolipid metabolism in malignant glioma

Kolar

Shi

Clay

et al. 2021

MRAJ

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Gliomas are the largest category of primary malignant brain tumors in adults, and glioblastomas account for nearly half of malignant gliomas. Glioblastomas are notoriously aggressive and drug-resistant, with a very poor 5 year survival rate of about 5%. New approaches to treatment are thus urgently needed. We previously identified an enzyme of fatty acid metabolism, very long-chain acyl-CoA synthetase 3 (ACSVL3), as a potential therapeutic target in glioblastoma. Using the glioblastoma cell line U87MG, we created a cell line with genomic deletion of ACSVL3 (U87-KO) and investigated potential mechanisms to explain how this enzyme supports the malignant properties of glioblastoma cells. Compared to U87MG cells, U87-KO cells grew slower and assumed a more normal morphology. They produced fewer, and far smaller, subcutaneous xenografts in nude mice. Acyl-CoA synthetases, including ACSVL3, convert fatty acids to their acyl-CoA derivatives, allowing participation in diverse downstream lipid pathways. We examined the effect of ACSVL3 depletion on several such pathways. Fatty acid degradation for energy production was not affected in U87-KO cells. Fatty acid synthesis, and incorporation of de novo synthesized fatty acids into membrane phospholipids needed for rapid tumor cell growth, was not significantly affected by lack of ACSVL3. In contrast, U87-KO cells exhibited evidence of altered sphingolipid metabolism. Levels of ceramides containing 18-22 carbon fatty acids were significantly lower in U87-KO cells. This paralleled the fatty acid substrate specificity profile of ACSVL3. The rate of incorporation of stearate, an 18-carbon saturated fatty acid, into ceramides was reduced in U87-KO cells, and proteomics revealed lower abundance of ceramide synthesis pathway enzymes. Sphingolipids, including gangliosides, are functional constituents of lipid rafts, membrane microdomains thought to be organizing centers for receptor-mediated signaling. Both raft morphology and ganglioside composition were altered by deficiency of ACSVL3. Finally, levels of sphingosine-1-phosphate, a sphingolipid signaling molecule, were reduced in U87-KO cells. We conclude that ACSVL3 supports the malignant behavior of U87MG cells, at least in part, by altering cellular sphingolipid metabolism.

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Downregulation of hepatoma-derived growth factor suppresses the malignant phenotype of U87 human glioma cells

Cited by 7 publications

References 28 publications

<p>Downregulation of HDGF inhibits the tumorigenesis of bladder cancer cells by inactivating the PI3K-AKT signaling pathway</p>

<p>Downregulation of HDGF inhibits the tumorigenesis of bladder cancer cells by inactivating the PI3K-AKT signaling pathway</p>

Irradiated fibroblasts promote epithelial–mesenchymal transition and HDGF expression of esophageal squamous cell carcinoma

Very long-chain acyl-CoA synthetase 3 mediates onco-sphingolipid metabolism in malignant glioma

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