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Histone deacetylase 6 (HDAC6) is emerging as a novel therapeutic target in cancer treatment. HDAC6 plays an important role in cell migration, cell transformation, and DNA damage response. Our and others' studies have linked HDAC6's functions and HDAC6's regulation to the mitogen-activated protein kinase (MAPK) pathways. In particular, HDAC6's activity has been found to be regulated by EGF-EGFR-Ras-Raf-MEK-ERK signaling. Inversely, HDAC6 has been reported to modulate the functions of EGFR and Ras. In this review, we summarize the literature on HDAC6 and MAPK pathways, and emphasize the interaction between HDAC6 and the ERK-MAPK signaling cascade.
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http://dx.doi.org/10.1615/critrevoncog.2014012484 | DOI Listing |
Mol Psychiatry
September 2025
Institute of Neurology, Sichuan Provincial People's Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, Sichuan, 610054, China.
Alzheimer's disease (AD), a leading cause of dementia, represents a critical unmet global medical need. While the precise mechanisms underlying AD pathogenesis remain elusive, increasing evidence underscores the pivotal role of neuroinflammation in driving cognitive impairment. N6-methyladenosine (m6A), an epigenetic modification regulating RNA metabolism, has been found to be dysregulated in AD.
View Article and Find Full Text PDFTrends Mol Med
September 2025
Institute of Pharmacology and Toxicology, University of Würzburg, 97078 Würzburg, Germany; Leibniz-Institut für Analytische Wissenschaften (ISAS) e.V., 44139 Dortmund, Germany. Electronic address:
Dysregulation of the RAF-MEK-ERK1/2 pathway is involved in the pathoetiology of many diseases. Its central role in cancer has led to the development of drugs targeting upstream receptors, RAS, and kinases in the extracellular signal-regulated kinase 1 (ERK1) and 2 (ERK2) signaling cascade. The use of these drugs in cancer therapy - together with ongoing monitoring of their effectiveness, evolving side-effects, and resistance mechanisms - has expanded our knowledge of both the physiological and pathological functions of ERK1/2 and could thus provide potential alternative therapeutic strategies.
View Article and Find Full Text PDFFish Shellfish Immunol
September 2025
State Key Laboratory of Breeding Biotechnology and Sustainable Aquaculture, State Key Laboratory of Aquaculture Disease Control, Ministry of Agriculture and Rural Affairs, Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan 430072, China; College of Advanced Agricultural Sciences, Universi
Metaflammation, a chronic immune response triggered by metabolic dysregulation, poses significant threats to gut-liver homeostasis in aquaculture species. To understand the progression of metaflammation, it is crucial to examine the role of SOCS8 deficiency in socs8 zebrafish, as this species may serve as a disease model for metabolic disorders due to the gradual dysregulation of immunity, metabolism, and the gut microbiota observed in them. This study examines the immune-metabolic crosstalk in grass carp, subjected to soybean meal-induced enteritis, and in socs8 zebrafish under genetic and dietary stress.
View Article and Find Full Text PDFToxicol Appl Pharmacol
September 2025
Department of Environmental Hygiene and Toxicology, School of Public Health, Wenzhou Medical University, Wenzhou 325035, China. Electronic address:
Phthalates (PEs) are widespread in environment, and human beings are unavoidably exposing to the mixture of PEs, which may induce male reproductive health risks. In order to investigate the mechanism of male reproductive injuries caused by the mixture of di-2-ethylhexyl phthalate, dibutyl phthalate and butyl benzyl phthalate (MPEs), male rats were orally exposed to 16 mg/kg/d MPEs (L-MPEs) and 450 mg/kg/d MPEs (H-MPEs) for 90 days, and the results showed that MPEs decreased the weights of testes, epididymis and periepididymis fat, decreased serum levels of male hormones, increased abnormal sperm rate, and caused testicular histopathological damages, such as atrophy and cavitation of seminiferous tubules, spermatids exfoliation, Leydig cells hyperplasia and accumulation of lipid droplets in the testicular interstitium. Testicular transcriptomic analysis identified 100 differently expressed genes (DEGs) in L-MPEs group and 10,880 DEGs in H-MPEs group, and these DEGs mainly involved in signaling pathways of focal adhesion, PI3K-Akt, AGE-RAGE, axon guidance, PPAR, MAPK and etc.
View Article and Find Full Text PDFBiochim Biophys Acta Rev Cancer
September 2025
Department of Neurosurgery, The First Hospital of China Medical University, Nanjing Street 155, Heping District, Shenyang 110001, PR China. Electronic address:
The complement system, a cornerstone of innate immunity, plays pivotal roles in both defense and pathology, particularly through its anaphylatoxins, C3a and C5a. These small peptides, generated during complement activation, not only mediate pro-inflammatory responses but also contribute to the progression of various cancers by modulating the tumor microenvironment (TME). Anaphylatoxins influence tumor cell proliferation, epithelial-mesenchymal transition, angiogenesis, immune suppression, and therapy resistance via key signaling pathways such as PI3K/AKT, MEK/ERK, and p38 MAPK.
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