Please use this identifier to cite or link to this item: https://doi.org/10.1084/jem.20170354
Title: EGF hijacks miR-198/FSTL1 wound-healing switch and steers a two-pronged pathway toward metastasis
Authors: Sundaram, G.M
Ismail, H.M
Bashir, M
Muhuri, M
Vaz, C
Nama, S
Ow, G.S
Vladimirovna, I.A
Ramalingam, R
Burke, B
Tanavde, V
Kuznetsov, V
Birgitte Lane, E
Sampath, P 
Keywords: actin related protein 2-3 complex
dIAPH1 protein
epidermal growth factor
follistatin
follistatin like 1
gelatinase B
microRNA
microRNA 198
mitogen activated protein kinase
unclassified drug
Wnt7a protein
epidermal growth factor
follistatin related protein
Fstl1 protein, mouse
microRNA
MIRN198 microRNA, human
MIRN198 microRNA, mouse
3' untranslated region
A-253 cell line
animal experiment
animal model
Article
cancer prognosis
cancer survival
carcinogenesis
cell lysate
cell migration
cell proliferation
competitive inhibition
controlled study
down regulation
enzyme activity
enzyme phosphorylation
enzyme synthesis
extracellular matrix
FaDu cell line
fluorescence in situ hybridization
gene expression
gene repression
gene switching
gene targeting
head and neck squamous cell carcinoma
human
human cell
immunohistochemistry
immunoprecipitation
in vivo study
metastasis
molecular pathology
mouse
nonhuman
overall survival
priority journal
protein protein interaction
RNA transcription
RNA translation
SCC-12 cell line
upregulation
Western blotting
wound healing
animal
cell transformation
female
head and neck tumor
mass spectrometry
metabolism
nonobese diabetic mouse
physiology
regulator gene
squamous cell carcinoma
wound healing
Animals
Blotting, Western
Carcinoma, Squamous Cell
Cell Proliferation
Cell Transformation, Neoplastic
Epidermal Growth Factor
Female
Follistatin-Related Proteins
Genes, Switch
Head and Neck Neoplasms
Immunoprecipitation
Mass Spectrometry
Mice, Inbred NOD
MicroRNAs
Wound Healing
Issue Date: 2017
Publisher: Rockefeller University Press
Citation: Sundaram, G.M, Ismail, H.M, Bashir, M, Muhuri, M, Vaz, C, Nama, S, Ow, G.S, Vladimirovna, I.A, Ramalingam, R, Burke, B, Tanavde, V, Kuznetsov, V, Birgitte Lane, E, Sampath, P (2017). EGF hijacks miR-198/FSTL1 wound-healing switch and steers a two-pronged pathway toward metastasis. Journal of Experimental Medicine 214 (10) : 2889-2900. ScholarBank@NUS Repository. https://doi.org/10.1084/jem.20170354
Rights: Attribution 4.0 International
Abstract: 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 (HNS CC ). This defect shuts off miR-198 expression in favor of sustained FSTL1 translation, driving metastasis through dual parallel pathways involving DIA PH1 and FSTL1. DIA PH1, 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-DIA PH1 gene pair makes it an attractive target for therapeutic intervention. © 2017 Sundaram et al.
Source Title: Journal of Experimental Medicine
URI: https://scholarbank.nus.edu.sg/handle/10635/179257
ISSN: 0022-1007
DOI: 10.1084/jem.20170354
Rights: Attribution 4.0 International
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