Reference Report

Reference
Citation	Igaki, T., Pagliarini, R.A., Xu, T. (2006). Loss of cell polarity drives tumor growth and invasion through JNK activation in Drosophila. Curr. Biol. 16(11): 1139--1146. (Export to RIS)
FlyBase ID	FBrf0194200
Publication Type	Research paper
PubMed ID	16753569
PubMed 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.
DOI	10.1016/j.cub.2006.04.042
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Supplementary material	Supplemental data. [FBrf0208877]
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Language of Publication	English
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Publication Type	Journal
Abbreviation	Curr. Biol.
Title	Current Biology
Publication Year	1991-
ISBN/ISSN	0960-9822
Data from Reference
Alleles (25)
	Akt1¹ Akt1^{Scer\UAS.T:Ivir\HA1} bsk^DN.Scer\UAS bsk^{dsRNA.Scer\UAS} dlg1¹⁴ Ecol\lacZ^puc-E69 egr^Scer\UAS.cIa hep^CA.Scer\UAS hep^NIG.4353R l(2)gl⁴ Pvr^{dsRNA.Scer\UAS} Ras85D^V12.Scer\UAS Scer\FLP1^ey.PN Scer\GAL4^Act5C.PI Scer\GAL4^GMR.PF Scer\GAL4^{Scer\FRT.Act5C} scrib¹ shg^k03401 shg^Scer\UAS.cOa Tak1^NIG.1388R Traf4^{dsRNA.Scer\UAS} Traf6^{dsRNA.Scer\UAS} Tsc1^Q600X wgn^{dsRNA.Scer\UAS} wts^x1
Constructs (16)
	P{Act5C-GAL4} P{AyGAL4} P{GAL4-ninaE.GMR} P{NIG.1388R} P{NIG.4353R} P{UAS-Akt1.HA} P{UAS-bsk.DN} P{UAS-bsk.IR} P{UAS-eiger.I} P{UAS-hep.CA} P{UAS-Pvr.IR} P{UAS-Ras85D.V12} P{UAS-shg.DECH} P{UAS-Traf1.IR} P{UAS-Traf6.IR} P{UAS-wengen-IR}
Genes (20)
	Akt1 bsk dlg1 Ecol\lacZ egr hep l(2)gl puc Pvr Ras85D Scer\FLP1 Scer\GAL4 scrib shg Tak1 Traf4 Traf6 Tsc1 wgn wts
Insertions (2)
	P{A92}puc^E69 P{lacW}shg^k03401
Natural transposons (1)
	P-element