Ras is one of the most commonly mutated oncogenes in the array of human cancers. The mechanism by which Ras induces cellular transformation is, however, not fully elucidated. We present here evidence that oncogenic Ras suppresses the expression of the tumor suppressor phosphatase and tensin homologue deleted from chromosome 10 (PTEN), and this action of oncogenic Ras is mediated by the Raf-mitogen-activated protein kinase/extracellular signal-regulated kinase (ERK) kinase (MEK)-ERK pathway via up-regulation of c-Jun. Jun(+/+) cells undergo cellular transformation by oncogenic Ras, and restoration of wild-type PTEN, but not a phosphate-defective mutant of PTEN, induces apoptosis in these cells. Conversely, in Jun(-/-) cells, oncogenic Ras neither suppresses PTEN nor causes transformation, but rather it induces PTEN-dependent apoptosis. An apoptotic response to oncogenic Ras in Jun(-/-) cells can be prevented by suppressing PTEN expression. These findings imply that oncogenic Ras suppresses the apoptotic gene PTEN via the Raf-MEK-ERK-c-Jun pathway to induce antiapoptosis and cellular transformation. Together, our findings identify a novel molecular interface between the oncogenic and tumor suppressor pathways that regulates cellular transformation and survival.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1158/0008-5472.CAN-07-1827 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
A Review of Circulating Tumor DNA (ctDNA) in Pancreatic Cancer: Ready for the Clinic?
J Gastrointest Cancer
January 2025
Ruesch Center for the Cure of Gastrointestinal Cancers, Lombardi Comprehensive Cancer Center, Georgetown University, Washington, DC, USA.
Pancreatic ductal adenocarcinoma is a devastating disease which is associated with an increase in cancer-related death in the USA. The minority of patients are cured by surgery alone and typically require adjuvant chemotherapy in order to improve clinical outcomes. Circulating tumor DNA (ctDNA) is an emerging technology whereby microscopic levels of minimal residual disease (MRD) can be detected in the bloodstream.
View Article and Find Full Text PDFA cost-effectiveness analysis of sotorasib as second-line treatment for patients with KRAS-G12C-mutated metastatic non-small cell lung cancer (mNSCLC) in Switzerland.
Swiss Med Wkly
January 2025
Cancer Center und Research Center, Cantonal Hospital Graubünden, Chur, Switzerland.
Background And Objective: Because of the lack of effective targeted treatment options, docetaxel has long been the standard second-line therapy for patients with advanced non-small cell lung cancer, including the Kirsten rat sarcoma virus (KRAS) G12C mutation. The CodeBreak 200 trial demonstrated that sotorasib, a new drug targeting the G12C-mutated KRAS protein, modestly improved progression-free survival compared with docetaxel in patients whose cancer had progressed after receiving platinum chemotherapy and programmed cell death protein 1 (PD-1) / programmed death ligand 1 (PD-L1) inhibitors as first-line treatment. Consequently, sotorasib received temporary approval in Switzerland.
View Article and Find Full Text PDFRIT1 Promotes the Proliferation of Gliomas Through the Regulation of the PI3K/AKT/c-Myc Signalling Pathway.
J Cell Mol Med
January 2025
Department of Anesthesiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Recently, RIT1 has been implicated in a range of neurological disorders; however, its precise function in glioma pathogenesis is not yet well-defined. This study employed quantitative reverse transcription PCR (qRT-PCR), Western blotting (WB), immunohistochemistry (IHC) and additional methodologies to assess RIT1 expression levels in glioma tissues. Furthermore, the study investigated its influence on glioma progression through a series of functional experiments.
View Article and Find Full Text PDFIntercellular TIMP-1-CD63 signaling directs the evolution of immune escape and metastasis in KRAS-mutated pancreatic cancer cells.
Mol Cancer
January 2025
Department of Physiology, College of Medicine, National Cheng Kung University, Tainan, Taiwan.
Background And Aims: Oncogenic KRAS mutations are present in approximately 90% of pancreatic ductal adenocarcinoma (PDAC). However, Kras mutation alone is insufficient to transform precancerous cells into metastatic PDAC. This study investigates how KRAS-mutated epithelial cells acquire the capacity to escape senescence or even immune clearance, thereby progressing to advanced PDAC.
View Article and Find Full Text PDFKEAP1 mutations as key crucial prognostic biomarkers for resistance to KRAS-G12C inhibitors.
J Transl Med
January 2025
Department of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, China.
Background: KRAS-G12C inhibitors mark a notable advancement in targeted cancer therapies, yet identifying predictive biomarkers for treatment efficacy and resistance remains essential for optimizing clinical outcomes.
Methods: This systematic meta-analysis synthesized studies available through September 2024 across PubMed, Cochrane Library, SpringerLink, and Embase. Using CRISPR/Cas9 technology, this study generated cells with KEAP1 and STK11 knockouts, and utilized lentiviral vectors to overexpress PD-L1.
Want AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!