Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.7.12.2 (MEK)
 18,161 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

To verify whether piceatannol-induced death of leukemia cells was associated with Fas-mediated death pathway, the present study was conducted. Piceatannol-induced apoptotic death of human leukemia U937 cells was characterized by increase in intracellular Ca(2+) concentration ([Ca(2+)]i), ERK inactivation, p38 MPAK activation, degradation of procaspase-8 and production of t-Bid. Piceatannol treatment increased Fas and FasL protein expression, and up-regulated transcription of Fas and FasL mRNA. Down-regulation of FADD blocked piceatannol-induced procaspase-8 degradation and rescued viability of piceatannol-treated cells. Abolition of piceatannol-induced increase in [Ca(2+)]i abrogated p38 MAPK activation and up-regulation of Fas and FasL expression, but restored ERK activation and viability of piceatannol-treated cells. Suppression of p38alpha MAPK or transfection of constitutively active MEK1 abolished piceatannol-induced Fas and FasL up-regulation. Piceatannol treatment repressed ERK-mediated c-Fos phosphorylation but evoked p38alpha MAPK-mediated c-Jun and ATF-2 phosphorylation. Knockdown of c-Fos, c-Jun and ATF-2 by siRNA reflected that c-Fos attenuated the effect of c-Jun and ATF-2 on Fas/FasL up-regulation. Taken together, our data indicate that Fas/FasL up-regulation in piceatannol-treated U937 cells is elicited by Ca(2+)/p38alpha MAPK-mediated activation of c-Jun and ATF-2, and suggest that autocrine Fas-mediated apoptotic mechanism is involved in piceatannol-induced cell death.
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PMID:Piceatannol induces Fas and FasL up-regulation in human leukemia U937 cells via Ca2+/p38alpha MAPK-mediated activation of c-Jun and ATF-2 pathways. 2058 Jun 78

Spleen tyrosine kinase (SYK), a non-receptor cytoplasmic tyrosine enzyme, is well known for its ability in certain pathways through immune receptors. Recently, SYK role in cancer has been widely studied. SYK plays a dual role as a tumor suppressor and tumor promoter. Nevertheless, its role in oral squamous cell carcinoma (OSCC) has not been fully investigated. In the current study, samples from OSCC tumors and adjacent normal counterparts were collected and SYK expression was evaluated by real-time qPCR. SYK mRNA expression in tumors was higher than the normal tissues. And high SYK expression was confirmed by immunohistochemistry analysis and closely related to worse overall survival. The expression of SYK mRNA and protein was detected in 2 of 4 OSCC cell lines. SYK pharmacological suppression and RNAi-mediated knockdown inhibited proliferation, migration, and invasion of SYK-positive cells by reducing phosphorylated ERK1/2 and mTOR levels. One inhibitor of MEK, PD98059, also suppressed the same cancer-associated phenotypes of SYK-positive cells by decreasing phosphorylated ERK1/2 but increasing phosphorylated mTOR. Piceatannol, one pharmacological inhibitor of SYK, attenuated tumor growth in vivo. Overall, our results revealed a novel mechanism triggered by SYK to increase OSCC tumoriogenesis and tumor progression.
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PMID:Activated spleen tyrosine kinase promotes malignant progression of oral squamous cell carcinoma via mTOR/S6 signaling pathway in an ERK1/2-independent manner. 2913 91