EGFR-dependent TOR-independent endocycles support Drosophila gut epithelial regeneration

Xiang, Jun; Bandura, Jennifer L.; Zhang, Peng; Jin, Yinhua; Reuter, Hanna; Edgar, Bruce A.

doi:10.1038/ncomms15125

Cited by 102 publications

(142 citation statements)

References 60 publications

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“…And in model systems of autocrine stimulation of EGFR, or EGFR overexpression and mutation, consequent transformation has been observed [26, 27]. EGFR may function through activating a network of signaling pathways, involving Ras, phosphoinositide 3-kinase and the signal transducer, activator of transcription family [28-30], and so forth in ccRCC [31, 32]. …”

Section: Discussionmentioning

confidence: 99%

LINC00037 Inhibits Proliferation of Renal Cell Carcinoma Cells in an Epidermal Growth Factor Receptor-Dependent Way

Gong

et al. 2018

Cell Physiol Biochem

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Background/Aims: LINC00037 has previously been reported to be up-regulated in clear cell renal cell carcinoma (ccRCC), however, the underlying mechanism remained unknown. In this study, we designed to investigate the functional role of LINC00037 in ccRCC Methods: LINC00037 knockdown and re-expressing 786-O and A498 cells were established. CCK8 assay and EdU assay were performed to evaluate the proliferation rates of ccRCC cells. Flow cytometry assay was performed to detect the cell apoptosis and cell cycle. Subcutaneous injection xenotransplantation mouse model was used to observe the role of LINC00037 in tumor growth in vivo. Mass spectrometry (MS) was performed to find the interacting partner of LINC00037 and RNA immunoprecipitation (RIP) was carried out to validate their interaction. Results: We found that knockdown of LINC00037 resulted in inhibited cell proliferation with activated apoptosis and cell cycle arrest in vitro. Over-expression of LINC00037 in LINC00037 knockdown cells restored and enhanced cell proliferation. In vivo mouse model indicated reduced tumor progression by LINC00037 depletion and promoted tumor progression by LINC00037 overexpression. LINC00037 could bind to epidermal growth factor receptor (EGFR) and increase the protein level of EGFR. Conclusion: LINC00037 could inhibit proliferation of ccRCC in an epidermal growth factor receptor-dependent way.

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Section: Discussionmentioning

confidence: 99%

LINC00037 Inhibits Proliferation of Renal Cell Carcinoma Cells in an Epidermal Growth Factor Receptor-Dependent Way

Gong

et al. 2018

Cell Physiol Biochem

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“…One possibility is by affecting levels of cell cycle regulators such as the transcription factor E2f1, which is essential for both mitotic and endoreplicative cell cycles (Davoli and de Lange, 2011, Fox and Duronio, 2013, Frawley and Orr-Weaver, 2015. This model is based on studies of the polyploid enterocytes of the adult midgut, in which activation of the MAPK pathway via the EGF receptor stabilizes E2f1 protein, leading to transcription activation of cyclin E (Xiang et al, 2017). Because restoring the polyploidization defect of kdm5 mutant prothoracic glands restored developmental timing but not lethality, this model would require that ectopic Torso/MAPK also impact the activity of additional cellular pathways in concert with, or independent from, a direct effect on cell cycle regulators.…”

Section: Discussionmentioning

confidence: 99%

The histone demethylase KDM5 controls developmental timing inDrosophilaby promoting prothoracic gland endocycles

Drelon

Belálcazar

Secombe

2019

Preprint

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In Drosophila, the larval prothoracic gland integrates nutritional status with developmental signals to regulate growth and maturation through the secretion of the steroid hormone ecdysone. While the nutritional signals and cellular pathways that regulate prothoracic gland function are relatively well studied, the transcriptional regulators that orchestrate the activity of this tissue remain largely unknown. Here we show that lysine demethylase 5 (KDM5) is essential for prothoracic gland function. Indeed, restoring kdm5 expression only in the prothoracic gland in an otherwise kdm5 mutant animal is sufficient to rescue both the larval developmental delay and the pupal lethality caused by loss of KDM5. Molecularly, our studies show that KDM5 functions by promoting the endoreplication of prothoracic gland cells, a process that increases ploidy and is rate-limiting for the expression of ecdysone biosynthetic genes. This occurs through KDM5-mediated regulation of the receptor tyrosine kinase torso, which in in turn promotes polyploidization and growth through activation of the MAPK signaling pathway. Taken together, our studies provide key insights into the biological processes regulated by KDM5 and the molecular mechanisms that govern the transcriptional regulation of animal development.

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“…Endoreplication, in addition to inefficient cell mitosis, contributes significantly to tissue regeneration upon damage. The JAK/STAT and the EGFR pathways are activated in both the Drosophila midgut stem cells to induce their mitosis and in EBs and young ECs to promote endoreplication (Jiang, 2009;Xiang, 2017). In the damaged adult epidermis, the Hippo pathway induces compensatory polyploidization, and in the hindgut, pylorus endoreplication increases in response to apoptosis (Losick, 2013).…”

Section: Introductionmentioning

confidence: 99%

Intertwined trade-offs coordinateDrosophilamidgut mitosis vs. endoreplication and host defense vs. dysplasia

Tamamouna

Panagi

Theophanous

et al. 2019

Preprint

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Inflammatory signaling supports host defense against infection, not only through immune cells, but also via regeneration of damaged tissue. Heightened regeneration, nevertheless, predisposes for all types of cancer and thus a trade-off exists between regeneration capacity and long-term tissue homeostasis. Here, we study the role of tissue-intrinsic regenerative inflammatory signaling in stem cell mitosis of the adult Drosophila midgut at the baseline and the infected state and its impact on intestinal host defense to infection and stem cell-mediated dysplasia. Through a quantitative genetics screen we find that stem cell mitosis is positively linked with the expression of eiger, Delta, upd3 and vein in the midgut, as well as with dysplasia and host defense, but negatively with enterocyte endoreplication. We provide evidence that intertwined trade-offs fine-tune midgut homeostasis, according to which stem cell mitosis through cyclin E in stem cells promotes the optimal host defense to infection, unless dysplasia ensues. However, cyclin E in enteroblasts promotes enterocyte endoreplication and counterbalances stem cell mitosis and dysplasia, providing an alternative but less efficient mechanism to support host defense.

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EGFR-dependent TOR-independent endocycles support Drosophila gut epithelial regeneration

Cited by 102 publications

References 60 publications

LINC00037 Inhibits Proliferation of Renal Cell Carcinoma Cells in an Epidermal Growth Factor Receptor-Dependent Way

LINC00037 Inhibits Proliferation of Renal Cell Carcinoma Cells in an Epidermal Growth Factor Receptor-Dependent Way

The histone demethylase KDM5 controls developmental timing inDrosophilaby promoting prothoracic gland endocycles

Intertwined trade-offs coordinateDrosophilamidgut mitosis vs. endoreplication and host defense vs. dysplasia

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