An adaptive signaling network in melanoma inflammatory niches confers tolerance to MAPK signaling inhibition
نویسندگان
چکیده
منابع مشابه
An adaptive signaling network in melanoma inflammatory niches confers tolerance to MAPK signaling inhibition
Mitogen-activated protein kinase (MAPK) pathway antagonists induce profound clinical responses in advanced cutaneous melanoma, but complete remissions are frustrated by the development of acquired resistance. Before resistance emerges, adaptive responses establish a mutation-independent drug tolerance. Antagonizing these adaptive responses could improve drug effects, thereby thwarting the emerg...
متن کاملData-Derived Modeling Characterizes Plasticity of MAPK Signaling in Melanoma
The majority of melanomas have been shown to harbor somatic mutations in the RAS-RAF-MEK-MAPK and PI3K-AKT pathways, which play a major role in regulation of proliferation and survival. The prevalence of these mutations makes these kinase signal transduction pathways an attractive target for cancer therapy. However, tumors have generally shown adaptive resistance to treatment. This adaptation i...
متن کاملInhibition of retinoic acid receptor β signaling confers glycolytic dependence and sensitization to dichloroacetate in melanoma cells
Dysregulation of metabolism during melanoma progression is tightly associated with the acquisition of genetic and epigenetic alterations in regulators of metabolic pathways. Retinoic acid receptor beta (RARβ) is epigenetically silenced in a large proportion of melanomas, but a link between RARβ and metabolic rewiring of melanoma has not been established. Here, we show that in primary human mela...
متن کاملProximal inhibition of p38 MAPK stress signaling prevents distal axonopathy.
The p38 mitogen-activated protein kinase (MAPK) isoforms are phosphorylated by a variety of stress stimuli in neurodegenerative disease and act as upstream activators of myriad pathogenic processes. Thus, p38 MAPK inhibitors are of growing interest as possible therapeutic interventions. Axonal dysfunction is an early component of most neurodegenerative disorders, including the most prevalent op...
متن کاملInhibition of p38 MAPK signaling promotes late stages of myogenesis.
Signaling through the p38 mitogen-activated protein kinases (MAPKs) is essential for cartilage formation in primary cultures of limb mesenchyme. Here we show that, concurrent with a decrease in chondrogenesis, inhibition of p38 in limb bud cultures dramatically promotes muscle development. Specifically, treatment of primary limb bud cultures with p38 inhibitors increases the expression of myoge...
متن کاملذخیره در منابع من
با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید
ژورنال
عنوان ژورنال: Journal of Experimental Medicine
سال: 2017
ISSN: 0022-1007,1540-9538
DOI: 10.1084/jem.20160855