ELOVL2 promotes cancer progression by inhibiting cell apoptosis in renal cell carcinoma

Metabolomics analysis possibly identifies new therapeutic targets in treatment resistance by measuring changes in metabolites accompanying cancer progression. We previously conducted a global metabolomics (G-Met) study of renal cell carcinoma (RCC) and identified metabolites that may be involved in sunitinib resistance in RCC. Here, we aimed to elucidate possible mechanisms of sunitinib resistance in RCC through intracellular metabolites. We established sunitinib-resistant and control RCC cell lines from tumor tissues of RCC cell (786-O)-injected mice. We also quantified characteristic metabolites identified in our G-Met study to compare intracellular metabolism between the two cell lines using liquid chromatography-mass spectrometry. The established sunitinib-resistant RCC cell line demonstrated significantly desuppressed protein kinase B (Akt) and mesenchymal-to-epithelial transition (MET) phosphorylation compared with the control RCC cell line under sunitinib exposure. Among identified metabolites, glutamine, glutamic acid, and α-KG (involved in glutamine uptake into the tricarboxylic acid (TCA) cycle for energy metabolism); fructose 6-phosphate, D-sedoheptulose 7-phosphate, and glucose 1-phosphate (involved in increased glycolysis and its intermediate metabolites); and glutathione and myoinositol (antioxidant effects) were significantly increased in the sunitinib-resistant RCC cell line. Particularly, glutamine transporter (SLC1A5) expression was significantly increased in sunitinib-resistant RCC cells compared with control cells. In this study, we demonstrated energy metabolism with glutamine uptake and glycolysis upregulation, as well as antioxidant activity, was also associated with sunitinib resistance in RCC cells.

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CD151 expression can predict cancer progression in clear cell renal cell carcinoma

Histopathology ◽

10.1111/j.1365-2559.2011.03752.x ◽

2011 ◽

Vol 58 (2) ◽

pp. 191-197 ◽

Cited By ~ 27

Author(s):

Seong H Yoo ◽

Kyoungbun Lee ◽

Ji Y Chae ◽

Kyung C Moon

Keyword(s):

Renal Cell Carcinoma ◽

Cell Carcinoma ◽

Cancer Progression ◽

Renal Cell ◽

Clear Cell ◽

Cell Renal Cell Carcinoma

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B7-H4 expression in renal cell carcinoma and tumor vasculature: Associations with cancer progression and survival

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.0600937103 ◽

2006 ◽

Vol 103 (27) ◽

pp. 10391-10396 ◽

Cited By ~ 214

Author(s):

A. E. Krambeck ◽

R. H. Thompson ◽

H. Dong ◽

C. M. Lohse ◽

E. S. Park ◽

...

Keyword(s):

Renal Cell Carcinoma ◽

Cell Carcinoma ◽

Cancer Progression ◽

Renal Cell ◽

Tumor Vasculature

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Identification Of Gene Signature For Renal Cell Carcinoma-Associated Fibroblasts Mediating Cancer Progression And Affecting Prognosis

10.21203/rs.3.rs-49601/v1 ◽

2020 ◽

Author(s):

Bitian Liu ◽

Xiaonan Chen ◽

Yunhong Zhan ◽

Bin Wu ◽

Shen Pan

Keyword(s):

Renal Cell Carcinoma ◽

Cell Carcinoma ◽

Single Cell ◽

Clinical Significance ◽

Cell Lines ◽

Cancer Progression ◽

Renal Cell ◽

Gene Signature ◽

Pathological Grade ◽

Single Cell Sequencing

Abstract Background: Cancer-associated fibroblasts (CAFs) are most abundant in stroma and are critically involved in cancer progression. However, the specific signature of CAFs and related clinicopathological parameters in renal cell carcinoma (RCC) remain unclear. Methods: In this work, methods using recognized gene signatures were employed to roughly assess the infiltration level of the stroma and CAFs in RCC based on the data in The Cancer Genome Atlas. Weighted gene co-expression network analysis (WGCNA) was used to cluster transcriptomes and correlate with CAFs to identify specific markers. A comparison of fibroblast versus urothelial carcinoma cell lines and correlation with previously reported CAF markers were performed to demonstrate the specific expressed of the gene signature. The gene signature was used to compare fibroblast infiltration of each sample through single sample gene set enrichment analysis, and the clinical significance of fibroblasts was analyzed via Cox risk assessment and the chi-square test. Finally, we used validation data to verify the clinical significance of the fibroblast gene signature in RCC. Results: Roughly calculated tumor matrix and CAF levels were significantly higher in kidney cancer than in normal tissues. More than 85% of fibroblast-specific markers identified by WGCNA were consistent with markers obtained via single-cell sequencing. These markers were more highly expressed in fibroblast cell lines and were significantly correlated with canonical CAFs makers. Data validation also showed that CAFs were significant correlation with survival and pathological grade. Conclusions: In summary, our findings indicate that the gene signature potentially serves as a biomarker of CAFs in RCC and that infiltration of fibroblasts in RCC is an independent prognostic factor associated with pathological grade and stage of tumor. The ability to recognize specific CAF markers using WGCNA is comparable to single-cell sequencing.

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Flotillin-1 expression in human clear-cell renal cell carcinoma is associated with cancer progression and poor patient survival

Molecular Medicine Reports ◽

10.3892/mmr.2014.2310 ◽

2014 ◽

Vol 10 (2) ◽

pp. 860-866 ◽

Cited By ~ 11

Author(s):

YIYAN ZHANG ◽

JIJUN LI ◽

YAN SONG ◽

FENGKUN CHEN ◽

YIN PEI ◽

...

Keyword(s):

Renal Cell Carcinoma ◽

Cell Carcinoma ◽

Cancer Progression ◽

Renal Cell ◽

Clear Cell ◽

Patient Survival ◽

Cell Renal Cell Carcinoma ◽

Poor Patient ◽

Poor Patient Survival

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Eg5 inhibitor, a novel potent targeted therapy, induces cell apoptosis in renal cell carcinoma

Tumor Biology ◽

10.1007/s13277-014-2022-x ◽

2014 ◽

Vol 35 (8) ◽

pp. 7659-7668 ◽

Cited By ~ 8

Author(s):

Sentai Ding ◽

Zuohui Zhao ◽

Dingqi Sun ◽

Fei Wu ◽

Dongbin Bi ◽

...

Keyword(s):

Renal Cell Carcinoma ◽

Targeted Therapy ◽

Cell Carcinoma ◽

Cell Apoptosis ◽

Renal Cell ◽

Eg5 Inhibitor

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Long Non-Coding RNA TUG1 Promotes Cell Proliferation and Inhibits Cell Apoptosis, Autophagy in Clear Cell Renal Cell Carcinoma via MiR-31-5p/FLOT1 Axis

OncoTargets and Therapy ◽

10.2147/ott.s254634 ◽

2020 ◽

Vol Volume 13 ◽

pp. 5857-5868

Author(s):

Dong Lv ◽

Ying Xiang ◽

Qi Yang ◽

Juncheng Yao ◽

Qiang Dong

Keyword(s):

Renal Cell Carcinoma ◽

Cell Proliferation ◽

Cell Carcinoma ◽

Cell Apoptosis ◽

Renal Cell ◽

Clear Cell ◽

Cell Renal Cell Carcinoma ◽

Non Coding Rna ◽

Long Non Coding Rna

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miR-21 Modulates Cell Apoptosis by Targeting Multiple Genes in Renal Cell Carcinoma

Urology ◽

10.1016/j.urology.2011.03.030 ◽

2011 ◽

Vol 78 (2) ◽

pp. 474.e13-474.e19 ◽

Cited By ~ 32

Author(s):

Aimin Zhang ◽

Yi Liu ◽

Yizhen Shen ◽

Youhe Xu ◽

Xiangtie Li

Keyword(s):

Renal Cell Carcinoma ◽

Cell Carcinoma ◽

Cell Apoptosis ◽

Renal Cell ◽

Multiple Genes

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Bromodomain-Containing Protein 4 (BRD4) Inhibition Sensitizes Palomid 529-Induced Anti-Renal Cell Carcinoma Cell Activity in Vitro and in Vivo

Cellular Physiology and Biochemistry ◽

10.1159/000494185 ◽

2018 ◽

Vol 50 (2) ◽

pp. 640-653 ◽

Cited By ~ 2

Author(s):

Zhao-yu Xing ◽

Yin Wang ◽

Long Cheng ◽

Jie Chen ◽

Xiao-zhou He ◽

...

Keyword(s):

Renal Cell Carcinoma ◽

Cell Growth ◽

Cell Carcinoma ◽

Cell Apoptosis ◽

Renal Cell ◽

Elisa Assay ◽

Dual Inhibitor ◽

Brd4 Inhibition

Background/Aims: Mammalian target of rapamycin (mTOR) is a valuable treatment target of renal cell carcinoma (RCC). Palomid 529 is a novel mTORC1/2 dual inhibitor. Methods: RCC cells were treated with different concentrations of Palomid 529. Cell survival was tested by MTT assay and clonogenicity assay. Cell proliferation was tested by BrdU ELISA assay. Cell apoptosis was tested by the Hoechst-33342 nuclei staining assay and Histone DNA ELISA assay. mTOR signaling was tested by Western blotting assay and co-immunoprecipitation (IP) assay. The SCID mouse 786-O xenograft model was established to test RCC cell growth in vivo. Results: Palomid 529 exerted cytotoxic, anti-proliferative and pro-apoptotic activities in 786-O RCC cells. Palomid 529 disassembled mTORC1/2, causing de-phosphorylation of mTORC1/2 substrates. Bromodomain-containing protein 4 (BRD4) is a primary resistant factor of Palomid 529. Palomid 529-induced 786-O cell apoptosis was sensitized by BRD4 inhibitors or BRD4 silencing, but inhibited with BRD4 over-expression. Palomid 529-induced cytotoxicity in the primary human RCC cells was negatively correlated with BRD4 expression level. In vivo, Palomid 529 i.p. administration inhibited 786-O xenograft tumor growth in SCID mice. Its anti-tumor activity was further sensitized by co-administration of the BRD4 inhibitor JQ1. Cconclusion: Palomid 529 inhibits RCC cell growth in vitro and in vivo. BRD4 inhibition could further sensitize Palomid 529 against RCC cells.

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