guanosine-triphosphate and Kidney-Neoplasms

Increasing studies reported that the serum- and glucocorticoid-inducible kinases (SGKs) contributed to the tumorigenesis of various cancer. In this article, we are aiming to explore the function of SGK2 in renal cell cancer (RCC).. In this study, the SGK2 expression was quantified by Western blot (WB) in multiple RCC cell lines. And in vitro SGK2 knockdown and overexpression experiments were also performed. In addition, molecular function analysis was performed using FunRich software V3. The Cancer Genome Atlas (TCGA) database was retrieved to verify the association between the SGK2 expression and the prognosis of RCC patients.. We found that SGK2 was up-regulated in RCC tissues compared with adjacent normal tissues, and the SGK2 expression also increased in various RCC cell lines compared to that in the normal epithelial cell line HK-2. Meanwhile, the SGK2 expression was significantly associated with the survival rate of RCC patients. Functional experiments showed that silencing SGK2 expression inhibited RCC cells proliferation, migration, colony formation and invasion abilities in vitro, whereas opposite results were uncovered after overexpressing SGK2 in RCC cells. Furthermore, functional analyses showed that SGK2 related genes were associated with protein serine/threonine kinase activity, guanosine triphosphatase (GTPase) activity, guanyl-nucleotide exchange factor activity, and motor activity. Protein interaction analysis identified that growth factor receptor-bound protein 2 (GRB2), one of the most important upstream components in the growth factor signaling pathway, was significantly enriched in SGK2 related genes. In addition, the WB assay validated that SGK2 could promote the phosphorylation of ERK 1/2 and AKT.. Our results suggested that SGK2 promoted RCC progression by mediating the phosphorylation of extracellular regulated protein kinases (ERK) 1/2 and Protein kinase B (AKT/PKB), indicating that SGK2 might serve as a potential prognostic marker and therapeutic target for renal cancer patients.

Topics: Carcinoma, Renal Cell; Cell Line, Tumor; Disease Progression; Extracellular Signal-Regulated MAP Kinases; Female; Guanosine Triphosphate; Humans; Immediate-Early Proteins; Kidney Neoplasms; Male; MAP Kinase Signaling System; Phosphorylation; Protein Serine-Threonine Kinases; Proto-Oncogene Proteins c-akt; Up-Regulation

Renal cell carcinoma (RCC) is the most common neoplasm of the kidney in adults, accounting for ~3% of adult malignancies. Understanding the underlying mechanism of RCC tumorigenesis is necessary to improve patient survival. The present study revealed that Taxol‑induced microtubule (MT) polymerization causes cell cycle arrest and an increase in guanosine triphosphate‑Ras homology gene family, member A (GTP‑RhoA) protein expression. Disruption of Taxol‑induced MT polymerization reversed GTP‑RhoA expression and cell cycle arrest. The localization and redistribution of MTs and RhoA were consistent in cells with MT bundles and those without. Decreased GTP‑RhoA had no marked effect on Taxol‑induced MT bundling, however, it reduced the proportion of cells in G2/M phase. Taken together, Taxol‑induced MT polymerization regulated the protein expression levels of GTP‑RhoA and cell cycle arrest. However, the alteration in GTP‑RhoA expression did not influence MT arrangement, suggesting that GTP‑RhoA serves a pivotal role in Taxol‑induced MT polymerization and cell cycle arrest in RCC.

Topics: Antineoplastic Agents, Phytogenic; Carcinoma, Renal Cell; Cell Cycle Checkpoints; Cell Line, Tumor; G2 Phase Cell Cycle Checkpoints; Guanosine Triphosphate; Humans; Kidney Neoplasms; Microtubules; Paclitaxel; Polymerization; rhoA GTP-Binding Protein; Tubulin

Mutations in the renal tumour suppressor protein, folliculin, lead to proliferative skin lesions, lung complications and renal cell carcinoma. Folliculin has been reported to interact with AMP-activated kinase, a key component of the mammalian target of rapamycin pathway. Most cancer-causing mutations lead to a carboxy-terminal truncation of folliculin, pointing to a functional importance of this domain in tumour suppression. We present here the crystal structure of folliculin carboxy-terminal domain and demonstrate that it is distantly related to differentially expressed in normal cells and neoplasia (DENN) domain proteins, a family of Rab guanine nucleotide exchange factors (GEFs). Using biochemical analysis, we show that folliculin has GEF activity, indicating that folliculin is probably a distantly related member of this class of Rab GEFs.

Topics: Amino Acid Sequence; Carcinoma, Renal Cell; Crystallography, X-Ray; Death Domain Receptor Signaling Adaptor Proteins; Electrophoresis, Polyacrylamide Gel; Guanine Nucleotide Exchange Factors; Guanosine Diphosphate; Guanosine Triphosphate; Humans; Kidney Neoplasms; Models, Molecular; Molecular Sequence Data; Mutation; Protein Structure, Secondary; Protein Structure, Tertiary; Proto-Oncogene Proteins; Sequence Homology, Amino Acid; Tumor Suppressor Proteins

Topics: Animals; Antineoplastic Agents; Apoptosis; Chromatography, High Pressure Liquid; Clinical Trials as Topic; Down-Regulation; Guanosine Triphosphate; History, 20th Century; Humans; Ischemia; Kidney Neoplasms; Leukemia; Models, Biological; Neoplasms; Ribavirin; Signal Transduction; Time Factors; Tumor Cells, Cultured