| Added by | lklinares |
|---|---|
| Group name | EquipeLL |
| Item Type | Journal Article |
| Title | Gamma-Glutamyltransferase 1 Promotes Clear Cell Renal Cell Carcinoma Initiation and Progression |
| Creator | Bansal et al. |
| Author | Ankita Bansal |
| Author | Danielle J. Sanchez |
| Author | Vivek Nimgaonkar |
| Author | David Sanchez |
| Author | Romain Riscal |
| Author | Nicolas Skuli |
| Author | M. Celeste Simon |
| Abstract | Clear cell renal cell carcinoma (ccRCC) is the most common subtype of kidney cancer. While the localized form of this disease can be treated surgically, advanced and metastatic stages are resistant to chemotherapies. Although more innovative treatments, such as targeted or immune-based therapies, exist, the need for new therapeutic options remains. ccRCC presents unique metabolic signatures and multiple studies have reported a significant increase in levels of reduced glutathione (GSH) and its precursors in ccRCC tumor samples compared with normal kidney tissues. These observations led us to investigate the effects of blocking the GSH pathway, particularly the gamma-glutamyltransferase 1 (GGT1) enzyme, in multiple ccRCC cell lines. In this study, we provide in vitro and in vivo evidence that GGT1/GSH pathway inhibition impacts ccRCC cell growth, through increased cell-cycle arrest. Of note, GGT1 inhibition also impairs ccRCC cell migration. Finally, pharmacologic GSH pathway inhibition decreases ccRCC cell proliferation and increases sensitivity to standard chemotherapy. Our results suggest that GGT1/GSH pathway inhibition represents a new strategy to overcome ccRCC chemoresistance. IMPLICATIONS: GGT1/GSH pathway inhibition represents a promising therapeutic strategy to overcome chemoresistance and inhibit progression of ccRCC tumors. |
| Publication | Molecular cancer research: MCR |
| Volume | 17 |
| Issue | 9 |
| Pages | 1881-1892 |
| Date | 2019-09 |
| Journal Abbr | Mol Cancer Res |
| Language | eng |
| DOI | 10.1158/1541-7786.MCR-18-1204 |
| ISSN | 1557-3125 |
| Library Catalog | PubMed |
| Extra | PMID: 31151999 PMCID: PMC6726546 |
| Tags | Carcinoma, Renal Cell, Cell Line, Tumor, Cell Movement, Cell Proliferation, Disease Progression, Drug Resistance, Neoplasm, Female, gamma-Glutamyltransferase, Gene Expression Regulation, Neoplastic, Glutathione, Humans, Kidney Neoplasms, original, Signal Transduction, Up-Regulation |
| Date Added | 2024/12/03 - 09:12:56 |
| Date Modified | 2024/12/03 - 09:12:56 |
| Notes and Attachments | PubMed entry (Attachment) Version acceptée (Attachment) |
Institut de Recherche en Cancérologie de
