MAP3Ks as central regulators of cell fate during development

Craig, Evisabel A.; Stevens, Mark V.; Vaillancourt, Richard; Camenisch, Todd D.

doi:10.1002/dvdy.21750

Cited by 108 publications

(82 citation statements)

References 149 publications

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“…MAPK pathways consist of three classes of protein kinases: MAPK, MAP2K, and MAP3K. MAP3Ks provide the specificity for stimulus-dependent activation of downstream kinases (34). To date, 21 MAP3Ks are known to activate MAP2Ks, but these have rarely been investigated in the pathogenesis of GC.…”

Section: Discussionmentioning

confidence: 99%

Apoptosis signal-regulating kinase 1 and cyclin D1 compose a positive feedback loop contributing to tumor growth in gastric cancer

Hayakawa

Hirata

Nakagawa

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

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Mitogen-activated protein kinase (MAPK) pathways regulate multiple cellular functions and are highly active in many types of human cancers. Apoptosis signal-regulating kinase 1 (ASK1) is an upstream MAPK involved in apoptosis, inflammation, and carcinogenesis. This study investigated the role of ASK1 in the development of gastric cancer. In human gastric cancer specimens, we observed increased ASK1 expression, compared to nontumor epithelium. Using a chemically induced murine gastric tumorigenesis model, we observed increased tumor ASK1 expression, and ASK1 knockout mice had both fewer and smaller tumors than wild-type (WT) mice. ASK1 siRNA inhibited cell proliferation through the accumulation of cells in G1 phase of the cell cycle, and reduced cyclin D1 expression in gastric cancer cells, whereas these effects were uncommon in other cancer cells. ASK1 overexpression induced the transcription of cyclin D1, through AP-1 activation, and ASK1 levels were regulated by cyclin D1, via the Rb-E2F pathway. Exogenous ASK1 induced cyclin D1 expression, followed by elevated expression of endogenous ASK1. These results indicate an autoregulatory mechanism of ASK1 in the development of gastric cancer. Targeting this positive feedback loop, ASK1 may present a potential therapeutic target for the treatment of advanced gastric cancer. JNK | c-JunG astric cancer (GC) is a common cancer worldwide, associated with a high mortality despite its declining incidence in recent decades. Smoking, salted or smoked foods, and Helicobacter pylori appear to be major environmental inducers of GC (1-3). Although the role of H. pylori in causing mucosal effects has been investigated, which molecular signal(s) initiate the program of irreversible transformation remain unclear, and thus molecular targeting therapies for GC have not been well established.Mitogen-activated protein kinase (MAPK) pathways are important for the development of gastric tumorigenesis (4). Apoptosis signal-regulating kinase 1 (ASK1) is a ubiquitously expressed MAPK kinase kinase (MAP3K), activated by various stress stimuli, including reactive oxygen species (ROS), TNF-α, and LPS (5-7). ASK1 activates the JNK and p38 signaling pathways and is required for both oxidative stress and cytokine-induced apoptosis (5). Furthermore, ASK1 affects multiple cellular functions, including survival, differentiation, and the innate immune response (5,7,8) and has been reported to be involved in the pathogenesis of various human diseases, including neurodegenerative (9), cardiovascular (10), and inflammatory diseases (11,12). Additionally, ASK1 has been shown to participate in both colon (12) and skin (13) tumorigenesis through the regulation of inflammation and apoptosis. However, no reported study has demonstrated a role for ASK1 in gastric tumorigenesis.In this study, we examined the role of ASK1 in gastric tumorigenesis using both human GC samples and ASK1-deficient (ASK1 −/− ) mice. We demonstrated that ASK1 is important for gastric tumorigenesis through the regulation of cyclin D1 e...

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Section: Discussionmentioning

confidence: 99%

Apoptosis signal-regulating kinase 1 and cyclin D1 compose a positive feedback loop contributing to tumor growth in gastric cancer

Hayakawa

Hirata

Nakagawa

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

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“…MAPK is vital in cell growth, differentiation, proliferation and apoptosis as an essential component of signal transduction (28). Certain studies have indicated that members of the MAPK signaling pathway, including ERK, p38 MAPK and JNK, are important in signal transduction pathways activated by stimuli and mediate a number of physiological and pathological changes in cell function (29).…”

Section: B Amentioning

confidence: 99%

Recombinant human brain natriuretic peptide attenuates LPS-induced cellular injury in human fetal lung fibroblasts via inhibiting MAPK and NF-κB pathway activation

Song

Zhao

Liu

et al. 2016

Molecular Medicine Reports

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Abstract. Inflammatory responses are vital in lung injury diseases, particularly acute respiratory distress syndrome (ARDS). Recombinant human brain natriuretic peptide (rhBNP) has been shown to exhibit anti-inflammatory effects in vivo in our previous studies. The present study aimed to investigate the mechanisms underlying the anti-inflammatory effects of rhBNP on lipopolysaccharide (LPS)-induced human fetal lung fibroblasts (HFL-1). The results showed that LPS induced a significant increase in the leakage of lactate dehydrogenase and the secretion of interleukin (IL)-1β. Activation of p38, extracellular-signal regulated kinase (ERK) 1/2, c-Jun NH2-terminal kinase (JNK) mitogen-activated protein kinases (MAPK)s, and nuclear factor (NF)-κB in HFL-1 cells was also observed following treatment with LPS. Treatment with rhBNP (0.1 µM) reduced the production of IL-1β at the protein and mRNA levels. Moreover, rhBNP decreased the phosphorylation of p38, ERK1/2 and JNK induced by LPS. However, the JNK inhibitor, SP600125, significantly inhibited LPS-induced IL-1β production. These results indicate that the inhibition of IL-1β by may dependent upon the JNK signaling pathway. The LPS-induced NF-κB activation was also suppressed by rhBNP, and IL-1β production was inhibited by the NF-κB inhibitor. Furthermore, NF-κB activation was attenuated by the JNK inhibitor, indicating that NF-κB activation was dependent on the JNK signaling pathway. The present study suggests that rhBNP exhibits an anti-inflammatory effect on LPS-induced HFL-1 cell injury via the inhibition of MAPK and NF-κB signaling pathways and may exhibit therapeutic potential for acute lung injury and ARDS.

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“…The regulation of Raf proteins including C-Raf is complex and involves various mechanisms (20,21,39); for instance, the activity of Raf is regulated by various factors including scaffolding proteins and heat shock proteins, in addition to Ras proteins. Furthermore, there are many kinases that can activate the MEK-ERK pathway in addition to Raf proteins in cells (39,40), and the MEK-ERK pathway in HeLa cells is regulated by endogenous Cot/tpl-2 (MAPKKK; Refs. 41,42).…”

mentioning

confidence: 99%

Activation of Cytosolic Phospholipase A2α by Epidermal Growth Factor (EGF) and Phorbol Ester in HeLa Cells: Different Effects of Inhibitors for EGF Receptor, Protein Kinase C, Src, and C-Raf

et al. 2009

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Abstract. In several types of cancer cells, prostaglandins produced via the over-expression of epidermal growth factor receptor (EGFR) and cyclooxygenases regulate cell growth. We investigated the signaling mechanisms for the release of arachidonic acid (AA, a precursor for prostaglandins) in human cervical carcinoma HeLa cells. Treatment with EGF and 4β-phorbol 12-myristate 13-acetate (PMA) with A23187 released AA accompanied by the phosphorylation of extracellular signal-regulated kinases (ERK1/2). Pharmacological experiments showed that the responses (ERK phosphorylation and AA release) induced by EGF and PMA were mediated by a mitogen-activated protein kinase /ERK kinase (MEK) -ERK -α-type cytosolic phospholipase A 2 (cPLA 2 α) pathway and that EGFR couples with the pathway in a manner insensitive to sorafenib, an inhibitor of B-and C-Raf, enzymes upstream of MEK. Activation of protein kinase C by PMA couples with the pathway partly in a sorafenib-sensitive and probably C-Raf-mediated manner and partly in a family of Src tyrosine kinases (Src)-dependent and sorafenib-insensitive manner. Co-treatment with sorafenib and an inhibitor of Src family members additionally inhibited the PMA-induced release of AA. Cross-talk between EGFR and protein kinase C was not observed. In human lung carcinoma A549 cells, the release of AA by EGF was insensitive to sorafenib. Possible mechanisms for the sorafenib-insensitive activation of the MEK-ERK-cPLA 2 α pathway are discussed.

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MAP3Ks as central regulators of cell fate during development

Cited by 108 publications

References 149 publications

Apoptosis signal-regulating kinase 1 and cyclin D1 compose a positive feedback loop contributing to tumor growth in gastric cancer

Apoptosis signal-regulating kinase 1 and cyclin D1 compose a positive feedback loop contributing to tumor growth in gastric cancer

Recombinant human brain natriuretic peptide attenuates LPS-induced cellular injury in human fetal lung fibroblasts via inhibiting MAPK and NF-κB pathway activation

Activation of Cytosolic Phospholipase A2α by Epidermal Growth Factor (EGF) and Phorbol Ester in HeLa Cells: Different Effects of Inhibitors for EGF Receptor, Protein Kinase C, Src, and C-Raf

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