scholarly journals Ectodermal Wnt controls nasal pit morphogenesis through modulation of the BMP/FGF/JNK signaling axis

2016 ◽  
Vol 245 (3) ◽  
pp. 414-426 ◽  
Author(s):  
Xiao-Jing Zhu ◽  
Yudong Liu ◽  
Xueyan Yuan ◽  
Min Wang ◽  
Wanxin Zhao ◽  
...  
Keyword(s):  
Jnk Signaling ◽  
Signaling Axis ◽  
Nasal Pit

scholarly journals miR-5591-5p regulates the effect of ADSCs in repairing diabetic wound via targeting AGEs/AGER/JNK signaling axis

2018 ◽  
Vol 9 (5) ◽  
Author(s):  
Qiang Li ◽  
Sizhan Xia ◽  
Yating Yin ◽  
Yanping Guo ◽  
Feifei Chen ◽  
...  
Keyword(s):  
Diabetic Wound ◽  
Jnk Signaling ◽  
Signaling Axis

scholarly journals Shikonin induces colorectal carcinoma cells apoptosis and autophagy by targeting galectin-1/JNK signaling axis

2020 ◽  
Vol 16 (1) ◽  
pp. 147-161 ◽  
Author(s):  
Nan Zhang ◽  
Fu Peng ◽  
Yujia Wang ◽  
Li Yang ◽  
Fengbo Wu ◽  
...  
Keyword(s):  
Colorectal Carcinoma ◽  
Carcinoma Cells ◽  
Jnk Signaling ◽  
Signaling Axis

AML Cells Utilize TNF-Driven JNK Signaling As a Critical NF-κB-Independent Survival Signal

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 2890-2890
Author(s):  
Andrew Volk ◽  
Jing Li ◽  
Junping Xin ◽  
Dewen You ◽  
Jun Zhang ◽  
...  
Keyword(s):  
Cell Death ◽  
Peripheral Blood ◽  
Leukemic Cells ◽  
Jnk Signaling ◽  
Survival Signal ◽  
Signaling Axis ◽  
Factor C ◽  
Inhibitor Treatment

Abstract Leukemic Stem Cells (LSCs) isolated from Acute Myeloid Leukemia (AML) patients are highly sensitive to NF-κB inhibition-induced cell death in in vitro culture when compared to normal hematopoietic stem/progenitor cells (HSPCs). This suggests blocking NF-κB could be an effective strategy for treating AML. However, NF-κB inhibitor treatment alone is unable to clear AML tumors in vivo. We propose this is most likely due to elements within the niche microenvironment stimulating compensatory survival/proliferation signals in AML cells that can overcome NF-κB inhibition. We utilize a multi-faceted AML model that includes a murine system created by MLL-AF9 transduced hematopoietic cells, several established human AML cell lines, and primary AML tumors isolated from patients. We observed elevated Tumor Necrosis Factor-α (TNF) levels in the peripheral blood of AML M3, 4, and 5 patients. Our studies suggest this TNF is produced directly by the AML cells, and that AML cells utilize TNF to stimulate JNK as a survival signal parallel to NF-κB in leukemic cells and a death signal in HSPCs. In healthy HSPCs, stimulation with exogenous TNF induces RIP1/3-mediated necroptosis and caspase-mediated apoptosis, resulting in cell death and loss of normal hematopoietic function. Inactivation of JNK signaling can partially rescue TNF-mediated loss of function in HSPCs. Additionally, blocking NF-κB in HSPCs sensitizes them to TNF-mediated cell death, which can also be partially prevented by inactivation of JNK signaling. These data suggest that JNK acts as a TNF-mediated death signal in HSPCs. In AML, we found TNF signaling promotes the in vitro growth of leukemic cells as well as enhancing the in vivo development of AML tumors by stimulation of both NF-κB and JNK signaling in parallel. We determined that TNF-mediated JNK signaling in leukemic cells results in the propagation of a critical survival signal. These cells convert TNF-JNK stimulation from a death to survival signal by limiting JNK activity duration as well as upregulating the expression of the AP1 family transcription factor c-Jun. Therefore, TNF-JNK signaling in leukemic cells does not drive apoptotic cell death, but instead drives c-Jun activity and the subsequent production of the anti-apoptotic genes c-Flip and Mcl-1. We found inactivation of any part of the TNF-JNK-AP1 signaling axis can repress the growth of leukemic cells in vitro and delay leukemogenesis in vivo. We also show that blocking any portion of the TNF-JNK-AP1 signaling axis sensitizes TNF-expressing leukemic cells, including LSCs, to NF-κB inhibitor treatment while at the same time protecting HSPCs from such treatment. In conclusion, our studies suggest that the inadequate ability of NF-κB inhibition to clear AML tumors in vivo is due to the TNF-mediated activation of the JNK-AP1 signaling axis that can compensate for NF-κB signal repression in LSCs. We found that many types of AMLs produce TNF, and this TNF acts both in an autocrine fashion to promote LSC survival and self-renewal through parallel activation of NF-κB and JNK-AP1, as well as in a paracrine fashion to repress normal hematopoiesis. Therefore, we propose that inhibition of both TNF-JNK-AP1 and NF-κB signals may provide a more thorough treatment for AML patients with elevated peripheral blood TNF. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Iron mitigates DMT1-mediated manganese cytotoxicity via the ASK1-JNK signaling axis: Implications of iron supplementation for manganese toxicity

2016 ◽  
Vol 6 (1) ◽  
Author(s):  
Yee Kit Tai ◽  
Katherine C. M. Chew ◽  
Bryce W. Q. Tan ◽  
Kah-Leong Lim ◽  
Tuck Wah Soong
Keyword(s):  
Iron Supplementation ◽  
Manganese Toxicity ◽  
Jnk Signaling ◽  
Signaling Axis

scholarly journals Nonphagocytic Oxidase 1 Causes Death in Lung Epithelial Cells via a TNF-RI–JNK Signaling Axis

2007 ◽  
Vol 36 (4) ◽  
pp. 473-479 ◽  
Author(s):  
Cristen Pantano ◽  
Vikas Anathy ◽  
Priya Ranjan ◽  
Nicholas H. Heintz ◽  
Yvonne M. W. Janssen-Heininger
Keyword(s):  
Epithelial Cells ◽  
Lung Epithelial Cells ◽  
Jnk Signaling ◽  
Lung Epithelial ◽  
Signaling Axis

scholarly journals The Small GTP-Binding Protein RhoA Regulates c-Jun by a ROCK-JNK Signaling Axis

2004 ◽  
Vol 14 (1) ◽  
pp. 29-41 ◽  
Author(s):  
Maria Julia Marinissen ◽  
Mario Chiariello ◽  
Tamara Tanos ◽  
Ora Bernard ◽  
Shuh Narumiya ◽  
...  
Keyword(s):  
Binding Protein ◽  
Gtp Binding Protein ◽  
Jnk Signaling ◽  
Gtp Binding ◽  
Signaling Axis

scholarly journals ERK2 regulates epithelial-to-mesenchymal plasticity through DOCK10-dependent Rac1/FoxO1 activation

2019 ◽  
Vol 116 (8) ◽  
pp. 2967-2976 ◽  
Author(s):  
Sejeong Shin ◽  
Gwen R. Buel ◽  
Michal J. Nagiec ◽  
Min-Joon Han ◽  
Philippe P. Roux ◽  
...  
Keyword(s):  
Gene Expression ◽  
Transcription Factor ◽  
Epithelial Cells ◽  
Epithelial To Mesenchymal Transition ◽  
Global Changes ◽  
Jnk Signaling ◽  
Mesenchymal Transition ◽  
Potential Mediator ◽  
Signaling Axis ◽  
Inducing Factors

ERK is a key coordinator of the epithelial-to-mesenchymal transition (EMT) in that a variety of EMT-inducing factors activate signaling pathways that converge on ERK to regulate EMT transcription programs. However, the mechanisms by which ERK controls the EMT program are not well understood. Through an analysis of the global changes of gene expression mediated by ERK2, we identified the transcription factor FoxO1 as a potential mediator of ERK2-induced EMT, and thus we investigated the mechanism by which ERK2 regulates FoxO1. Additionally, our analysis revealed that ERK2 induced the expression of Dock10, a Rac1/Cdc42 GEF, during EMT. We demonstrate that the activation of the Rac1/JNK signaling axis downstream of Dock10 leads to an increase in FoxO1 expression and EMT. Taken together, our study uncovers mechanisms by which epithelial cells acquire less proliferative but more migratory mesenchymal properties and reveals potential therapeutic targets for cancers evolving into a metastatic disease state.

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