What a tangled web we weave: crosstalk between JAK–STAT and other signalling pathways during development in Drosophila

FEBS Journal, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 16, 2025

The Janus kinase-signal transducer and activator of transcription (JAK-STAT) signalling pathway is a key player in animal development physiology. Although it functions variety processes, the net output JAK-STAT depends on its spatiotemporal activation, as well extensive crosstalk with other pathways. Drosophila, relatively simple signal transduction pathways plethora genetic analysis tools, an ideal system for dissecting interactions. In this review, we explore studies Drosophila revealing that lies at nexus complex network interlinked pathways, including epidermal growth factor receptor (EGFR), c-Jun N-terminal kinase (JNK), Notch, Insulin, Hippo, bone morphogenetic protein (BMP), Hedgehog (Hh) Wingless (Wg). These can synergise or antagonise one another to produce outcomes. Given conserved nature conclude our perspective implication dysregulation human diseases, how have potential inform influence clinical research.

Language: Английский

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Shared enhancer gene regulatory networks between wound and oncogenic programs

eLife, Journal Year: 2023, Volume and Issue: 12

Published: May 3, 2023

Wound response programs are often activated during neoplastic growth in tumors. In both wound repair and tumor growth, cells respond to acute stress balance the activation of multiple programs, including apoptosis, proliferation, cell migration. Central those responses JNK/MAPK JAK/STAT signaling pathways. Yet, what extent these cascades interact at cis-regulatory level how they orchestrate different regulatory phenotypic is still unclear. Here, we aim characterize states that emerge cooperate response, using Drosophila melanogaster wing disc as a model system, compare with cancer induced by rasV12scrib-/- eye disc. We used single-cell multiome profiling derive enhancer gene networks (eGRNs) integrating chromatin accessibility expression signals. identify 'proliferative' eGRN, active majority wounded controlled AP-1 STAT. smaller, but distinct population cells, 'senescent' eGRN driven C/EBP-like transcription factors (Irbp18, Xrp1, Slow border, Vrille) Scalloped. These two signatures found be levels. Our eGRNs resource offers an in-depth characterization senescence markers, together new perspective on shared acting oncogenesis.

Language: Английский

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The impact of nitric oxide on HER family post-translational modification and downstream signaling in cancer

Frontiers in Physiology, Journal Year: 2024, Volume and Issue: 15

Published: March 27, 2024

The human epidermal growth factor receptor (HER) family consists of four members, activated by two families ligands. They are known for mediating cell–cell interactions in organogenesis, and their deregulation has been associated with various cancers, including breast esophageal cancers. In particular, aberrant (EGFR) HER2 signaling drive disease progression result poorer patient outcomes. Nitric oxide (NO) proposed as an alternative activator the HER may play a role this activation due to its ability induce s-nitrosation phosphorylation EGFR. This review discusses potential impact NO on downstream signaling, along efficacy therapeutics targeting family.

Language: Английский

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An unscheduled switch to endocycles induces a reversible senescent arrest that impairs growth of the Drosophila wing disc

PLoS Genetics, Journal Year: 2024, Volume and Issue: 20(9), P. e1011387 - e1011387

Published: Sept. 3, 2024

A programmed developmental switch to G / S endocycles results in tissue growth through an increase cell size. Unscheduled, induced endocycling cells (iECs) promote wound healing but also contribute cancer. Much remains unknown, however, about how these iECs affect growth. Using the D . melanogaster wing disc as model, we find that populations of initially size then subsequently undergo a heterogenous arrest causes severe undergrowth. acquired DNA damage and activated Jun N-terminal kinase (JNK) pathway, but, unlike other stressed cells, were apoptosis-resistant not eliminated from epithelium. Instead, entered JNK-dependent reversible senescent-like arrest. Senescent promoted division diploid neighbors, this compensatory proliferation did rescue Our study has uncovered unique attributes their effects on have important implications for understanding roles

Language: Английский

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Assessment of cytisine as an insecticide candidate for Hyphantria cunea management: Toxicological, biochemical, and control potential insights

Pesticide Biochemistry and Physiology, Journal Year: 2023, Volume and Issue: 196, P. 105638 - 105638

Published: Oct. 5, 2023

Language: Английский

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An unscheduled switch to endocycles induces a reversible senescent arrest that impairs growth of theDrosophilawing disc

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: March 14, 2024

Summary A programmed developmental switch to G / S endocycles results in tissue growth through an increase cell size. Unscheduled, induced endocycling cells (iECs) promote wound healing but also contribute cancer. Much remains unknown, however, about how these iECs affect growth. Using the D. melanogaster wing disc as model, we find that populations of initially size then subsequently undergo a heterogenous arrest causes severe undergrowth. acquired DNA damage and activated Jun N-terminal kinase (JNK) pathway, but, unlike other stressed cells, were apoptosis-resistant not eliminated from epithelium. Instead, entered JNK-dependent reversible senescent-like arrest. Senescent promoted division diploid neighbors, this compensatory proliferation did rescue Our study has uncovered unique attributes their effects on have important implications for understanding roles

Language: Английский

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Regeneration following tissue necrosis is mediated by non-apoptotic caspase activity

Published: Feb. 21, 2025

Tissue necrosis is a devastating complication for many human diseases and injuries. Unfortunately, our understanding of how it impacts surrounding healthy tissue – an essential consideration when developing effective methods to treat such injuries has been limited by lack robust genetically tractable models. Our lab previously established method study necrosis-induced regeneration in the Drosophila wing imaginal disc, which revealed unique phenomenon whereby cells at distance from injury upregulate caspase activity process called Necrosis-induced Apoptosis (NiA) that vital regeneration. Here we have further investigated this phenomenon, showing NiA predominantly associated with highly regenerative pouch region shaped genetic factors present presumptive hinge. Furthermore, find proportion fail undergo apoptosis, instead surviving effector activation persist within stimulate reparative proliferation late This relies on initiator Dronc, occurs independent JNK, ROS or mitogens characterized Apoptosis-induced Proliferation (AiP) mechanism. These data reveal new means non-apoptotic Dronc signaling promotes response necrotic damage.

Language: Английский

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Regeneration following tissue necrosis is mediated by non-apoptotic caspase activity

eLife, Journal Year: 2025, Volume and Issue: 13

Published: March 5, 2025

Tissue necrosis is a devastating complication for many human diseases and injuries. Unfortunately, our understanding of how it impacts surrounding healthy tissue – an essential consideration when developing effective methods to treat such injuries has been limited by lack robust genetically tractable models. Our lab previously established method study necrosis-induced regeneration in the Drosophila wing imaginal disc, which revealed unique phenomenon whereby cells at distance from injury upregulate caspase activity process called Necrosis-induced Apoptosis (NiA) that vital regeneration. Here, we have further investigated this phenomenon, showing NiA predominantly associated with highly regenerative pouch region shaped genetic factors present presumptive hinge. Furthermore, find proportion fail undergo apoptosis, instead surviving effector activation persist within stimulate reparative proliferation late This relies on initiator Dronc, occurs independent JNK, ROS or mitogens characterized Apoptosis-induced Proliferation (AiP) mechanism. These data reveal new means non-apoptotic Dronc signaling promotes response necrotic damage.

Language: Английский

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Activation of a Src-JNK pathway in unscheduled endocycling cells of the Drosophila wing disc induces a chronic wounding response

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2025, Volume and Issue: unknown

Published: March 13, 2025

Abstract The endocycle is a specialized cell cycle during which cells undergo repeated G / S phases to replicate DNA without division, leading large polyploid cells. transition from mitotic an can be triggered by various stresses, results in unscheduled, or induced endocycling (iECs). While iECs beneficial for wound healing, they also detrimental impairing tissue growth promoting cancer. However, the regulation of and its role remain poorly understood. Using Drosophila wing disc as model, we previously demonstrated that iEC arrested through Jun N-Terminal Kinase (JNK)-dependent, reversible senescence-like response. it remains unclear how JNK activated impact overall structure. In this study, performed genetic screen identified Src42A-Shark-Slpr pathway upstream regulator iECs, their arrest. We found tissues recognize wounds, releasing wound-related signals induce JNK-dependent developmental delay. Similar closure, response triggers Src-JNK-mediated actomyosin remodeling, yet persist rather than being eliminated. Our findings suggest shares key signaling cytoskeletal regulatory mechanisms with healing dorsal process embryogenesis. because are retained within tissue, create unique system may serve model studying chronic wounds tumor progression. Article summary effects unscheduled endocycles on unclear. To investigate this, used switch analyzed responses at both structure levels. Surprisingly, recognized activating regeneration remodeling these resist apoptosis, cleared. This persistence disrupts normal revealing similarities between wounds. has potential novel tumorigenesis.

Language: Английский

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Oncogenic signaling in the Drosophila prostate-like accessory gland activates a pro-tumorigenic program in the absence of proliferation

Disease Models & Mechanisms, Journal Year: 2025, Volume and Issue: 18(4)

Published: April 1, 2025

ABSTRACT Drosophila models for tumorigenesis have revealed conserved mechanisms of signaling involved in mammalian cancer. Many these use highly mitotically active tissues. Few adult tissues, when most cells are terminally differentiated and postmitotic. The accessory glands prostate-like a model prostate using this tissue has been explored. In prior model, oncogenic was induced during the proliferative stages gland development, raising question how activity impacts differentiated, postmitotic tissue. Here, we show that leads to activation pro-tumorigenic program, similar mitotic but absence proliferation. our experiments, led hypertrophy with nuclear anaplasia, part through endoreduplication. Oncogene-induced gene expression changes overlapped those polyploid cancer after chemotherapy, which potentially mediate tumor recurrence. Thus, provide useful aspects progression lack cellular

Language: Английский

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