Regulation of growth factor dependent cell survival is crucial for development and disease progression. Here, we report a novel function of Src kinases as a negative regulator of platelet-derived growth factor (PDGF) dependent cell survival. We characterized a series of PDGF alpha receptor (PDGFRA) mutants, which lack the binding sites for Src, phosphatidylinositol 3'-kinase (PI3K), SHP-2 or phospholipase C-gamma. We found that PDGFRA-dependent cell survival was mainly mediated through activation of PI3K, and was negatively regulated by Src. Characterization of the downstream signaling events revealed that PI3K activates the protein kinase Akt, which in turn phosphorylates and thus inactivates proapoptotic Forkhead transcription factors. Src phosphorylates the ubiquitin-ligase c-Cbl, which is required for degradation of the activated receptor. Consequently, overexpression of c-Cbl prevented PDGFRA-mediated cell survival, whereas it did not affect this response, when Src was unable to associate with the receptor. This novel function of Src in antiapoptotic signaling introduces Src kinases as an interesting therapeutic target in apoptosis related diseases.
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http://dx.doi.org/10.1016/j.febslet.2006.11.034 | DOI Listing |
Clin Transl Oncol
December 2024
Lillian S Wells Department of Neurosurgery at the University of Florida: University of Florida Lillian S Wells Department of Neurosurgery, Gainesville, FL, USA.
Glioblastoma (GBM) is one of the most common primary malignant brain tumors. Annually, there are about six instances recorded per 100,000 inhabitants. Treatment for GB has not advanced all that much.
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December 2024
School of Clinical Medicine, Dali University, Dali, 671000, Yunnan, People's Republic of China.
Objective: Searching for potential biomarkers and therapeutic targets for early diagnosis of gynecological tumors to improve patient survival.
Methods: Microarray datasets of cervical cancer (CC) and ovarian cancer (OC) were downloaded from the Gene Expression Omnibus (GEO) database, then, differential gene expression between cancerous and normal tissues in the datasets was analyzed. Weighted gene co-expression network analysis (WGCNA) was performed to screen for co-expression modules associated with CC and OC.
Discov Oncol
December 2024
Department of Neurosurgery, West China Hospital of Sichuan University, No. 37, Guoxue Lane, Wuhou District, Chengdu, China.
Background: Gliomas, particularly glioblastoma (GBM), are the most common and aggressive primary brain tumors in adults, characterized by high malignancy and frequent recurrence. Despite standard treatments, including surgery, radiotherapy, and chemotherapy, the prognosis for GBM remains poor, with a median survival of less than 15 months and a five-year survival rate below 10%. Tumor heterogeneity and resistance to treatment create significant challenges in controlling glioma progression.
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December 2024
Department of Radiation Oncology, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, China.
Background: Low-grade glioma (LGG) is a slow-growing but invasive tumor that affects brain function. Histone deacetylases (HDACs) play a critical role in gene regulation and tumor progression. This study aims to develop a prognostic model based on HDAC-related genes to aid in risk stratification and predict therapeutic responses.
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December 2024
Department of Thoracic Surgery, Shanghai University of Medicine & Health Sciences Affiliated Zhoupu Hospital, No. 1500 Zhouyuan Road, Pudong New Area, Shanghai, China.
Lung adenocarcinoma (LUAD) is a common histologic lung cancer with high morbidity and mortality, and most patients have distant metastases at diagnosis. RasGEF Domain Family Member 1C (RASGEF1C) could regulated Alzheimer's disease. However, its function in various cancers, including LUAD, is poorly understood.
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