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Acute myeloid leukemia (AML) is a hematologic malignant disease largely affecting older adults with poor outcomes. Lack of effective targeted treatment is a major challenge in managing the disease in the clinic. Scaffolding adaptor Gab2 is amplified in a subset of AML. However, the causative role of Gab2 in AML remains to be explored. In this study, it was found that Gab2 was expressed at high levels in AML patient samples and AML cell lines. Experiments by knocking down Gab2 expression using shRNA showed that Gab2 promoted AML cell growth and migration in vitro and in vivo. Further studies using Gab2 mutants and pharmacological inhibitors revealed that Gab2 increased CREB phosphorylation via the SHP-2/Erk signaling pathway. CREB phosphorylation contributed to Gab2-induced cell migration by increasing MMP2 and MMP9 expression. This research indicates that high Gab2 expression promotes AML progression through the SHP2-Erk-CREB signaling pathway. CREB suppression may help treat AML with high Gab2 expression.
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http://dx.doi.org/10.1002/JLB.2A0421-221R | DOI Listing |
Haematologica
September 2025
Center for Cardiometabolic Science, Christina Lee Brown Envirome Institute, Division of Environmental Medicine, Department of Medicine, University of Louisville, Louisville, Kentucky,.
Maintaining a healthy pool of circulating red blood cells (RBCs) is essential for adequate perfusion, as even minor changes in the population can impair oxygen delivery, resulting in serious health complications including tissue ischemia and organ dysfunction. This responsibility largely falls to specialized macrophages in the spleen, known as red pulp macrophages, which efficiently take up and recycle damaged RBCs. However, questions remain regarding how these macrophages are acutely activated to accommodate increased demand.
View Article and Find Full Text PDFCephalalgia
September 2025
Department of Molecular Physiology and Biophysics, University of Iowa, Iowa City, IA, USA.
Migraine is a complex neurological disorder involving multiple neuropeptides that modulate nociceptive and sensory pathways. The most studied peptide is calcitonin gene-related peptide (CGRP), which is a well-established migraine trigger and therapeutic target. Recently, another peptide, pituitary adenylate cyclase-activating polypeptide (PACAP), has emerged as an alternative target for migraine therapeutics.
View Article and Find Full Text PDFInsect Sci
September 2025
Hubei Key Laboratory of Resources Utilization and Sustainable Pest Management, College of Plant Science and Technology, Huazhong Agricultural University, Wuhan, China.
Phototaxis is a critical behavior in insects and is closely linked to vision and environmental adaptation. Understanding how insects perceive light and exhibit phototactic responses is crucial for assessing the ecological impact of artificial light at night. However, the molecular and neural mechanisms that regulate phototactic responses in insects remain largely unknown.
View Article and Find Full Text PDFActa Biochim Biophys Sin (Shanghai)
September 2025
Kinesin family member 14 (KIF14) has been implicated in the progression of multiple cancer types, yet its role in colorectal cancer (CRC) metastasis remains undefined. Here, we assesse KIF14 expression in CRC specimens and explore its clinical and functional significance. KIF14 upregulation is frequently observed in CRC tissues and is correlated with advanced tumor stage and reduced overall survival.
View Article and Find Full Text PDFJ Neurochem
September 2025
Center for Neurodegeneration and Experimental Therapeutics, Department of Neurology, University of Alabama at Birmingham, Birmingham, Alabama, USA.
Microglia, the resident immune cells of the central nervous system (CNS), are involved in the pathogenesis of neurodegenerative diseases, such as Alzheimer's disease (AD), Dementia with Lewy Bodies (DLB), and Parkinson's disease (PD). 14-3-3 proteins act as molecular hubs to regulate protein-protein interactions, which are involved in numerous cellular functions, including cellular signaling, protein folding, and apoptosis. We previously revealed decreased 14-3-3 levels in the brains of human subjects with neurodegenerative diseases.
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