Next-Generation Sequencing Reveals Increased Anti-oxidant Response and Ecdysone Signaling in STAT Supercompetitors in <i>Drosophila</i>

Sitaram, Poojitha; Lu, Sean; Harsh, Sneh; Herrera, Salvador C.; Bach, Erika A.

doi:10.1534/g3.119.400345

Cited by 3 publications

(4 citation statements)

References 90 publications

(132 reference statements)

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“…Among the conditions we re-analyzed, dilp8 induction was consistently very strong, with the exception of the ph tumors, ranging from 3.23-fold in Ras V12 + scrib- leg discs to an over 1000-fold induction in Ras V12 + scrib- wing discs ( Figure 1 ). dilp8 is a verified Yki/Sd target gene, but it can also be induced by JNK or JAK/STAT activation [ 63 , 64 , 65 ]. Notably, in cases where Yki is not activated, such as in Psc-Su(z)2 mutants, dilp8 is still heavily induced, showing that it can be induced independently of Yki activation ( Figure 1 ).…”

Section: Analysis/resultsmentioning

confidence: 99%

“…JAK/STAT activity can be assessed by expression of its best studied target gene, Suppressor of Cytokine Signaling at 36E (Socs36E) in various contexts [42,65,[102][103][104]. Socs36E acts as a feedback inhibitor of the pathway and can be used to test the contribution of JAK/STAT activity to tumors.…”

Section: Jak/stat Pathwaymentioning

confidence: 99%

“…Several other direct targets of the pathway have been identified and verified by the Bach Lab over the years, including chronologically inappropriate morphogenesis (chinmo), cap-n-collar (cnc), lamina ancestor (lama), Zn finger homeodomain 2 (zfh2), NADPH oxidase (Nox), Keap1 I (Keap1), and pannier (pnr) [65,101,107,108]. Among these, Nox, Keap1, and pnr are negatively regulated by the pathway and thus are shown in bold and traced in red ( Figure 6).…”

Section: Jak/stat Pathwaymentioning

confidence: 99%

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Rounding up the Usual Suspects: Assessing Yorkie, AP-1, and Stat Coactivation in Tumorigenesis

Hamaratoǧlu

Atkins

2020

IJMS

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Can hyperactivation of a few key signaling effectors be the underlying reason for the majority of epithelial cancers despite different driver mutations? Here, to address this question, we use the Drosophila model, which allows analysis of gene expression from tumors with known initiating mutations. Furthermore, its simplified signaling pathways have numerous well characterized targets we can use as pathway readouts. In Drosophila tumor models, changes in the activities of three pathways, Jun N-terminal Kinase (JNK), Janus Kinase/Signal Transducer and Activator of Transcription (JAK/STAT), and Hippo, mediated by AP-1 factors, Stat92E, and Yorkie, are reported frequently. We hypothesized this may indicate that these three pathways are commonly deregulated in tumors. To assess this, we mined the available transcriptomic data and evaluated the activity levels of eight pathways in various tumor models. Indeed, at least two out of our three suspects contribute to tumor development in all Drosophila cancer models assessed, despite different initiating mutations or tissues of origin. Surprisingly, we found that Notch signaling is also globally activated in all models examined. We propose that these four pathways, JNK, JAK/STAT, Hippo, and Notch, are paid special attention and assayed for systematically in existing and newly developed models.

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Section: Analysis/resultsmentioning

confidence: 99%

Section: Jak/stat Pathwaymentioning

confidence: 99%

Section: Jak/stat Pathwaymentioning

confidence: 99%

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Rounding up the Usual Suspects: Assessing Yorkie, AP-1, and Stat Coactivation in Tumorigenesis

Hamaratoǧlu

Atkins

2020

IJMS

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“…Second, ChIP-seq experiments in Drosophila embryonic Kc cells have shown that Myc does indeed bind to the chinmo locus [79]. Finally, chinmo levels are upregulated in response to elevated Myc expression in wing imaginal discs [80]. To determine whether chinmo expression was altered in brat 1 /+ wing discs, we immunostained for Chinmo protein.…”

Section: Loss Of Cell-fate Specification May Be Due To Misregulation ...mentioning

confidence: 99%

Regenerative growth is constrained by brain tumor to ensure proper patterning in Drosophila

Abidi,

Hsu,

Smith-Bolton

2023

PLoS Genet

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Some animals respond to injury by inducing new growth to regenerate the lost structures. This regenerative growth must be carefully controlled and constrained to prevent aberrant growth and to allow correct organization of the regenerating tissue. However, the factors that restrict regenerative growth have not been identified. Using a genetic ablation system in the Drosophila wing imaginal disc, we have identified one mechanism that constrains regenerative growth, impairment of which also leads to erroneous patterning of the final appendage. Regenerating discs with reduced levels of the RNA-regulator Brain tumor (Brat) exhibit enhanced regeneration, but produce adult wings with disrupted margins that are missing extensive tracts of sensory bristles. In these mutants, aberrantly high expression of the pro-growth factor Myc and its downstream targets likely contributes to this loss of cell-fate specification. Thus, Brat constrains the expression of pro-regeneration genes and ensures that the regenerating tissue forms the proper final structure.

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Regenerative growth is constrained bybrain tumorto ensure proper patterning inDrosophila

Abidi

Smith-Bolton

2019

Preprint

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1 2 Regeneration after injury happens in a complex environment that requires precise 3 orchestration of cell proliferation and establishment of correct patterning and cell-fate 4 specification to ensure a fully functional outcome. Regenerative growth needs to be 5 controlled and constrained to prevent overgrowth and to allow differentiation. However, 6 the factors that are required to restrict regeneration to facilitate patterning of the 7 regenerating tissue and establishment of correct cell fates have not been identified. 8Using a genetic ablation system in the Drosophila wing imaginal disc, we have identified 9 the gene brain tumor (brat) as a protective factor that shields the regenerating tissue 10 from excessive pro-growth gene activation and enables correct patterning and cell-fate 11 specification. Regenerating discs with reduced levels of brat are unable to pattern 12 correctly resulting in adult wings with a disrupted wing margin. This mis-patterning is 13 due to elevated levels of the pro-growth factor Myc and the self-renewal factor Chinmo, 14 which lead to suppression of the cell fate-specification gene cut (ct). Thus, Brat protects 15 regenerating tissue from erroneous patterning by constraining expression of pro-16 regeneration genes. 17 18 Introduction 19Regeneration is the remarkable process by which some organisms replace tissues and 20 organs after damage such that both morphology and function are restored. Complete 21 regeneration requires several steps to occur correctly including wound healing, cell 22 the process of regeneration was traditionally thought to be a redeployment of earlier 31 developmental steps (9,(26)(27)(28)(29). However, recent evidence suggests that regeneration is 32 not a simple reiteration of development but can employ regeneration-specific regulatory 33 mechanisms (3,25,(30)(31)(32)(33)(34). Indeed, faithful regeneration likely requires additional 34 mechanisms, since regrowth happens in the presence of wound-response signaling and 35 in a developed juvenile or adult organism. Additionally, pro-growth pathways that are 36 used during normal development are often activated in new ways and at higher 37 strengths in the regenerating tissue (2,7,15,23). These augmented pro-growth signals 38 must decline as regeneration progresses to prevent unrestrained growth and to enable 39 re-establishment of pattern and cell-fate specification. Thus, regeneration-specific 40 growth suppressors and additional patterning factors are likely used to terminate 41 regeneration and allow differentiation (reviewed in 35). However, despite our 42 understanding of the pro-growth signals needed for regeneration, we do not yet know 43 what distinct regeneration-specific factors exist in different model organisms to restrain 44 growth and promote re-patterning of regenerating tissue. 45 4 46 Drosophila melanogaster imaginal discs, precursors of adult fly appendages, are simple 47 columnar epithelia that have well-characterized, complex expression of patterning 48 genes that determine cell-fate spe...

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Next-Generation Sequencing Reveals Increased Anti-oxidant Response and Ecdysone Signaling in STAT Supercompetitors in Drosophila

Cited by 3 publications

References 90 publications

Rounding up the Usual Suspects: Assessing Yorkie, AP-1, and Stat Coactivation in Tumorigenesis

Rounding up the Usual Suspects: Assessing Yorkie, AP-1, and Stat Coactivation in Tumorigenesis

Regenerative growth is constrained by brain tumor to ensure proper patterning in Drosophila

Regenerative growth is constrained bybrain tumorto ensure proper patterning inDrosophila

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