Bendless modulates JNK-mediated cell death and migration in Drosophila

Ma, Xianjue; Li, W; Yu, Hua; Yang, Yanan; Li, M; Xue, Lei; Xu, Tian

doi:10.1038/cdd.2013.154

Cited by 53 publications

(61 citation statements)

References 47 publications

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“…In the Drosophila wing epithelia, knocking down the cell polarity gene scribbled (scrib) along the anterior/posterior boundary using a patched-Gal4 (ptc-Gal4) driver produces an invasive migration phenotype (17)(18)(19), which has been used to model cell invasion in vivo. First, to investigate whether Hippo signaling activation could modulate cell invasion, we overexpressed Hpo or Wts, or knocked down yki, by ptc-Gal4.…”

Section: Resultsmentioning

confidence: 99%

“…For experiments involving Hpo and Wts overexpression, tub-Gal80ts was used, flies were first raised at 18°C to restrict Gal4 activity for 5 d, then shifted to 29°C for 2 d to inactivate Gal80ts. The following strains were used for this study: ptc-Gal4, UAS-GFP, UAS-Dcr2, tub-Gal80ts, nd Rox8 EP were obtained from the Bloomington Stock Center; UAS-yki RNAi (#40497) was obtained from the Vienna Drosophila RNAi Center; UAS-Rox8 (GS17980) was a GS line obtained from the Kyoto Drosophila Genetic Resource Center; UAS-DIAP1, UAS-DRONC DN , Df(3L)H99, UAS-hep RNAi, UAS-Bsk DN (41), UAS-Egr, UAS-dTAK1 RNAi, UAS-dTRAF2 RNAi (17), UAS-wnd RNAi (18), UAS-Ban (55) were previously described; and UAS-dMyc (gift from Peter Gallant, University of Würzburg, Wuerzburg, Germany), UAS-ban-sp (bantam sponge, gift from Marco Milán, The Barcelona Institute of Science and Technology, Barcelona), UAS-Hpo and UAS-Wts (gifts from Shian Wu, Nankai University, Tianjin, China), upd > GFP (gift from Erika A. Bach, New York University School of Medicine).…”

Section: Methodsmentioning

confidence: 99%

“…MMP1 is a direct transcriptional target of JNK signaling (24), and JNK activation has been shown to play a critical role in modulating cell invasion (17,18,(24)(25)(26). Thus, we hypothesized that the Hippo pathway might regulate cell invasion through activating JNK signaling.…”

Section: Significancementioning

confidence: 99%

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Hippo signaling promotes JNK-dependent cell migration

Wang

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

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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.Hippo | JNK | Drosophila | migration | Rox8

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Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

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Hippo signaling promotes JNK-dependent cell migration

Wang

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

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“…Fluorescently labeled clones were produced in the eye discs as previously described (Pagliarini and Xu, 2003) using the following strains: tub -Gal80, FRT19A; ey - Flp5 , Act > y + >Gal4, UAS -GFP (19A tester); ey - Flp1 ; tub -Gal80, FRT40A; Act>y + >Gal4, UAS -GFP (40A tester); ey - Flp1 ; Act>y + >Gal4, UAS -GFP; tub -Gal80, FRT79E (79E tester); eyFlp1 ; Act > y + >Gal4, UAS -GFP.S65T; FRT82B, tub -Gal80 (82B tester). Additional strains, including KG09672, GMR -Gal4, ptc -Gal4, nub -Gal4, UAS -GFP, UAS-msn-IR, UAS-PpV (#53770) were obtained from Bloomington Drosophila Stock Center; UAS -dTAK1 DN , UAS-dTRAF2-IR (Xue et al, 2007), puc E69 , UAS -Egr, lgl 4 , UAS - Ras V12 , UAS -Puc (Ma et al, 2014), UAS -Bsk DN , UAS-hep-IR (Ma et al, 2015), scrib 1 (Igaki et al, 2009) were previously described. UAS-PpV-IR (V31690) and UAS-Fmt-IR (V16005) were obtained from the Vienna Drosophila RNAi Center; UAS -PpV HA (F000874) was obtained from FlyORF.…”

Section: Methodsmentioning

confidence: 99%

PP6 Disruption Synergizes with Oncogenic Ras to Promote JNK-Dependent Tumor Growth and Invasion

Dong

et al. 2017

Cell Reports

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Summary RAS genes are frequently mutated in cancers, yet an effective treatment has not been developed. This is partly due to an incomplete understanding of signaling within Ras-related tumors. To address this, we performed a genetic screen in Drosophila, aiming to find mutations that cooperate with oncogenic Ras (RasV12) to induce tumor overgrowth and invasion. We identified fiery mountain (fmt), a regulatory subunit of the protein phosphatase 6 (PP6) complex, as a tumor suppressor that synergizes with RasV12 to drive JNK-dependent tumor growth and invasiveness. We show that Fmt negatively regulates JNK upstream of dTAK1. We further demonstrate that disruption of PpV, the catalytic subunit of PP6, mimics fmt loss of function induced tumorigenesis. Finally, Fmt synergizes with PpV to inhibit JNK-dependent tumor progression. Our data here further highlight the power of Drosophila as a model system to unravel molecular mechanisms that may be relevant to human cancer biology.

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“…JNK signaling is also required for tumor growth triggered by loss of cell polarity and oncogenic Ras cooperation in Drosophila (8,9), and for progenitor cell proliferation and Ras-induced tumorigenesis in mammals (10,11).…”

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confidence: 99%

Impaired Hippo signaling promotes Rho1–JNK-dependent growth

Chen

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

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The Hippo and c-Jun N-terminal kinase (JNK) pathway both regulate growth and contribute to tumorigenesis when dysregulated. Whereas the Hippo pathway acts via the transcription coactivator Yki/YAP to regulate target gene expression, JNK signaling, triggered by various modulators including Rho GTPases, activates the transcription factors Jun and Fos. Here, we show that impaired Hippo signaling induces JNK activation through Rho1. Blocking Rho1–JNK signaling suppresses Yki-induced overgrowth in the wing disk, whereas ectopic Rho1 expression promotes tissue growth when apoptosis is prohibited. Furthermore, Yki directly regulates Rho1 transcription via the transcription factor Sd. Thus, our results have identified a novel molecular link between the Hippo and JNK pathways and implicated the essential role of the JNK pathway in Hippo signaling-related tumorigenesis.

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Bendless modulates JNK-mediated cell death and migration in Drosophila

Cited by 53 publications

References 47 publications

Hippo signaling promotes JNK-dependent cell migration

Hippo signaling promotes JNK-dependent cell migration

PP6 Disruption Synergizes with Oncogenic Ras to Promote JNK-Dependent Tumor Growth and Invasion

Impaired Hippo signaling promotes Rho1–JNK-dependent growth

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