RRC ID 11150
Author Igaki T, Pagliarini RA, Xu T.
Title Loss of cell polarity drives tumor growth and invasion through JNK activation in Drosophila.
Journal Curr. Biol.
Abstract Apparent defects in cell polarity are often seen in human cancer. However, the underlying mechanisms of how cell polarity disruption contributes to tumor progression are unknown. Here, using a Drosophila genetic model for Ras-induced tumor progression, we show a molecular link between loss of cell polarity and tumor malignancy. Mutation of different apicobasal polarity genes activates c-Jun N-terminal kinase (JNK) signaling and downregulates the E-cadherin/beta-catenin adhesion complex, both of which are necessary and sufficient to cause oncogenic Ras(V12)-induced benign tumors in the developing eye to exhibit metastatic behavior. Furthermore, activated JNK and Ras signaling cooperate in promoting tumor growth cell autonomously, as JNK signaling switches its proapoptotic role to a progrowth effect in the presence of oncogenic Ras. Our finding that such context-dependent alterations promote both tumor growth and metastatic behavior suggests that metastasis-promoting mutations may be selected for based primarily on their growth-promoting capabilities. Similar oncogenic cooperation mediated through these evolutionarily conserved signaling pathways could contribute to human cancer progression.
Volume 16(11)
Pages 1139-46
Published 2006-6-6
DOI 10.1016/j.cub.2006.04.042
PII S0960-9822(06)01539-9
PMID 16753569
MeSH Animals Apoptosis / genetics Cadherins / metabolism Cell Polarity / genetics Disease Models, Animal Drosophila / enzymology* Drosophila / genetics Drosophila / growth & development Drosophila Proteins / genetics Drosophila Proteins / metabolism* Drosophila Proteins / physiology Enzyme Activation Eye / pathology JNK Mitogen-Activated Protein Kinases / genetics JNK Mitogen-Activated Protein Kinases / metabolism* JNK Mitogen-Activated Protein Kinases / physiology Neoplasm Metastasis Neoplasms, Experimental / enzymology* Neoplasms, Experimental / genetics Neoplasms, Experimental / pathology Proto-Oncogene Proteins p21(ras) / metabolism Signal Transduction beta Catenin / metabolism
IF 9.193
Times Cited 162