Acetaminophen disrupts memory in object recognition and increases extracellular signal-regulated kinase phosphorylation in male mice.

2018 ◽  
Vol 132 (6) ◽  
pp. 580-586
Author(s):  
Tyler M. Milewski ◽  
Patrick T. Orr
Keyword(s):  
Object Recognition ◽  
Male Mice ◽  
Extracellular Signal Regulated Kinase ◽  
Extracellular Signal ◽  
Kinase Phosphorylation

scholarly journals EGF hijacks miR-198/FSTL1 wound-healing switch and steers a two-pronged pathway toward metastasis

2017 ◽  
Vol 214 (10) ◽  
pp. 2889-2900 ◽  
Author(s):  
Gopinath M. Sundaram ◽  
Hisyam M. Ismail ◽  
Mohsin Bashir ◽  
Manish Muhuri ◽  
Candida Vaz ◽  
...  
Keyword(s):  
Wound Healing ◽  
Wound Closure ◽  
Prognostic Significance ◽  
Competitive Inhibitor ◽  
Molecular Switch ◽  
Extracellular Signal Regulated Kinase ◽  
Keratinocyte Migration ◽  
Extracellular Signal ◽  
Single Transcript ◽  
Kinase Phosphorylation

Epithelial carcinomas are well known to activate a prolonged wound-healing program that promotes malignant transformation. Wound closure requires the activation of keratinocyte migration via a dual-state molecular switch. This switch involves production of either the anti-migratory microRNA miR-198 or the pro-migratory follistatin-like 1 (FSTL1) protein from a single transcript; miR-198 expression in healthy skin is down-regulated in favor of FSTL1 upon wounding, which enhances keratinocyte migration and promotes re-epithelialization. Here, we reveal a defective molecular switch in head and neck squamous cell carcinoma (HNSCC). This defect shuts off miR-198 expression in favor of sustained FSTL1 translation, driving metastasis through dual parallel pathways involving DIAPH1 and FSTL1. DIAPH1, a miR-198 target, enhances directional migration through sequestration of Arpin, a competitive inhibitor of Arp2/3 complex. FSTL1 blocks Wnt7a-mediated repression of extracellular signal–regulated kinase phosphorylation, enabling production of MMP9, which degrades the extracellular matrix and facilitates metastasis. The prognostic significance of the FSTL1-DIAPH1 gene pair makes it an attractive target for therapeutic intervention.

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