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• W3195333844 endingPage "e1009738" @default.
• W3195333844 startingPage "e1009738" @default.
• W3195333844 abstract "Activation of Ras signaling occurs in ~30% of human cancers. However, activated Ras alone is insufficient to produce malignancy. Thus, it is imperative to identify those genes cooperating with activated Ras in driving tumoral growth. In this work, we have identified a novel EGFR inhibitor, which we have named EGFRAP, for EGFR adaptor protein. Elimination of EGFRAP potentiates activated Ras-induced overgrowth in the Drosophila wing imaginal disc. We show that EGFRAP interacts physically with the phosphorylated form of EGFR via its SH2 domain. EGFRAP is expressed at high levels in regions of maximal EGFR/Ras pathway activity, such as at the presumptive wing margin. In addition, EGFRAP expression is up-regulated in conditions of oncogenic EGFR/Ras activation. Normal and oncogenic EGFR/Ras-mediated upregulation of EGRAP levels depend on the Notch pathway. We also find that elimination of EGFRAP does not affect overall organogenesis or viability. However, simultaneous downregulation of EGFRAP and its ortholog PVRAP results in defects associated with increased EGFR function. Based on these results, we propose that EGFRAP is a new negative regulator of the EGFR/Ras pathway, which, while being required redundantly for normal morphogenesis, behaves as an important modulator of EGFR/Ras-driven tissue hyperplasia. We suggest that the ability of EGFRAP to functionally inhibit the EGFR pathway in oncogenic cells results from the activation of a feedback loop leading to increase EGFRAP expression. This could act as a surveillance mechanism to prevent excessive EGFR activity and uncontrolled cell growth." @default.
• W3195333844 created "2021-08-30" @default.
• W3195333844 creator A5004157437 @default.
• W3195333844 creator A5034114861 @default.
• W3195333844 creator A5051121414 @default.
• W3195333844 creator A5064700337 @default.
• W3195333844 creator A5074137472 @default.
• W3195333844 date "2021-08-19" @default.
• W3195333844 modified "2023-10-13" @default.
• W3195333844 title "EGFRAP encodes a new negative regulator of the EGFR acting in both normal and oncogenic EGFR/Ras-driven tissue morphogenesis" @default.
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• W3195333844 doi "https://doi.org/10.1371/journal.pgen.1009738" @default.
• W3195333844 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/8407591" @default.
• W3195333844 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/34411095" @default.
• W3195333844 hasPublicationYear "2021" @default.
• W3195333844 type Work @default.
• W3195333844 sameAs 3195333844 @default.

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