Journal
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Volume 114, Issue 8, Pages 1934-1939Publisher
NATL ACAD SCIENCES
DOI: 10.1073/pnas.1621359114
Keywords
Hippo; JNK; Drosophila; migration; Rox8
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Funding
- National Natural Science Foundation of China [31371490, 31571516, 31601024, 81572501, 81572626]
- Shanghai Committee of Science and Technology [09DZ2260100]
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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 epithelialmesenchymal 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 Hipporelated cancers, as simply inhibiting Yorkie or YAP activity might paradoxically accelerate cell invasion and metastasis.
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