Feb 9, 2017

Hippo signaling promotes JNK-dependent cell migration

Proceedings of the National Academy of Sciences of the United States of America
Xianjue MaLei Xue

Abstract

Overwhelming studies show that dysregulation of the Hippo pathway is positively correlated with cell proliferation, growth, and tumorigenesis. Paradoxically, the detailed molecular roles of the Hippo pathway in cell invasion remain debatable. Using a Drosophila invasion model in wing epithelium, we show herein that activated Hippo signaling promotes cell invasion and epithelial-mesenchymal transition through JNK, as inhibition of JNK signaling dramatically blocked Hippo pathway activation-induced matrix metalloproteinase 1 expression and cell invasion. Furthermore, we identify bantam-Rox8 modules as essential components downstream of Yorkie in mediating JNK-dependent cell invasion. Finally, we confirm that YAP (Yes-associated protein) expression negatively regulates TIA1 (Rox8 ortholog) expression and cell invasion in human cancer cells. Together, these findings provide molecular insights into Hippo pathway-mediated cell invasion and also raise a noteworthy concern in therapeutic interventions of Hippo-related cancers, as simply inhibiting Yorkie or YAP activity might paradoxically accelerate cell invasion and metastasis.

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  • Citations8

References

Mentioned in this Paper

MAP2K1 protein, human
Interstitial Collagenase
Neuro-Oncological Ventral Antigen 2
Peptide Nucleic Acids
Real-Time Polymerase Chain Reaction
Study
Polar Bodies
Biochemical Pathway
Gene Expression Regulation, Neoplastic
Subfamily lentivirinae

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