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Bilateral JNK activation is a hallmark of interface surveillance and promotes elimination of aberrant cells

Tissue-intrinsic defense mechanisms eliminate aberrant cells from epithelia and thereby maintain the health of developing tissues or adult organisms. ‘Interface surveillance’ comprises one such distinct mechanism that specifically guards against aberrant cells which undergo inappropriate cell fate a...

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Autores principales: Prasad, Deepti, Illek, Katharina, Fischer, Friedericke, Holstein, Katrin, Classen, Anne-Kathrin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: eLife Sciences Publications, Ltd 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9917460/
https://www.ncbi.nlm.nih.gov/pubmed/36744859
http://dx.doi.org/10.7554/eLife.80809
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author Prasad, Deepti
Illek, Katharina
Fischer, Friedericke
Holstein, Katrin
Classen, Anne-Kathrin
author_facet Prasad, Deepti
Illek, Katharina
Fischer, Friedericke
Holstein, Katrin
Classen, Anne-Kathrin
author_sort Prasad, Deepti
collection PubMed
description Tissue-intrinsic defense mechanisms eliminate aberrant cells from epithelia and thereby maintain the health of developing tissues or adult organisms. ‘Interface surveillance’ comprises one such distinct mechanism that specifically guards against aberrant cells which undergo inappropriate cell fate and differentiation programs. The cellular mechanisms which facilitate detection and elimination of these aberrant cells are currently unknown. We find that in Drosophila imaginal discs, clones of cells with inappropriate activation of cell fate programs induce bilateral JNK activation at clonal interfaces, where wild type and aberrant cells make contact. JNK activation is required to drive apoptotic elimination of interface cells. Importantly, JNK activity and apoptosis are highest in interface cells within small aberrant clones, which likely supports the successful elimination of aberrant cells when they arise. Our findings are consistent with a model where clone size affects the topology of interface contacts and thereby the strength of JNK activation in wild type and aberrant interface cells. Bilateral JNK activation is unique to ‘interface surveillance’ and is not observed in other tissue-intrinsic defense mechanisms, such as classical ‘cell-cell competition’. Thus, bilateral JNK interface signaling provides an independent tissue-level mechanism to eliminate cells with inappropriate developmental fate but normal cellular fitness. Finally, oncogenic Ras-expressing clones activate ‘interface surveillance’ but evade elimination by bilateral JNK activation. Combined, our work establishes bilateral JNK interface signaling and interface apoptosis as a new hallmark of interface surveillance and highlights how oncogenic mutations evade tumor suppressor function encoded by this tissue-intrinsic surveillance system.
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spelling pubmed-99174602023-02-11 Bilateral JNK activation is a hallmark of interface surveillance and promotes elimination of aberrant cells Prasad, Deepti Illek, Katharina Fischer, Friedericke Holstein, Katrin Classen, Anne-Kathrin eLife Cancer Biology Tissue-intrinsic defense mechanisms eliminate aberrant cells from epithelia and thereby maintain the health of developing tissues or adult organisms. ‘Interface surveillance’ comprises one such distinct mechanism that specifically guards against aberrant cells which undergo inappropriate cell fate and differentiation programs. The cellular mechanisms which facilitate detection and elimination of these aberrant cells are currently unknown. We find that in Drosophila imaginal discs, clones of cells with inappropriate activation of cell fate programs induce bilateral JNK activation at clonal interfaces, where wild type and aberrant cells make contact. JNK activation is required to drive apoptotic elimination of interface cells. Importantly, JNK activity and apoptosis are highest in interface cells within small aberrant clones, which likely supports the successful elimination of aberrant cells when they arise. Our findings are consistent with a model where clone size affects the topology of interface contacts and thereby the strength of JNK activation in wild type and aberrant interface cells. Bilateral JNK activation is unique to ‘interface surveillance’ and is not observed in other tissue-intrinsic defense mechanisms, such as classical ‘cell-cell competition’. Thus, bilateral JNK interface signaling provides an independent tissue-level mechanism to eliminate cells with inappropriate developmental fate but normal cellular fitness. Finally, oncogenic Ras-expressing clones activate ‘interface surveillance’ but evade elimination by bilateral JNK activation. Combined, our work establishes bilateral JNK interface signaling and interface apoptosis as a new hallmark of interface surveillance and highlights how oncogenic mutations evade tumor suppressor function encoded by this tissue-intrinsic surveillance system. eLife Sciences Publications, Ltd 2023-02-06 /pmc/articles/PMC9917460/ /pubmed/36744859 http://dx.doi.org/10.7554/eLife.80809 Text en © 2023, Prasad et al https://creativecommons.org/licenses/by/4.0/This article is distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use and redistribution provided that the original author and source are credited.
spellingShingle Cancer Biology
Prasad, Deepti
Illek, Katharina
Fischer, Friedericke
Holstein, Katrin
Classen, Anne-Kathrin
Bilateral JNK activation is a hallmark of interface surveillance and promotes elimination of aberrant cells
title Bilateral JNK activation is a hallmark of interface surveillance and promotes elimination of aberrant cells
title_full Bilateral JNK activation is a hallmark of interface surveillance and promotes elimination of aberrant cells
title_fullStr Bilateral JNK activation is a hallmark of interface surveillance and promotes elimination of aberrant cells
title_full_unstemmed Bilateral JNK activation is a hallmark of interface surveillance and promotes elimination of aberrant cells
title_short Bilateral JNK activation is a hallmark of interface surveillance and promotes elimination of aberrant cells
title_sort bilateral jnk activation is a hallmark of interface surveillance and promotes elimination of aberrant cells
topic Cancer Biology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9917460/
https://www.ncbi.nlm.nih.gov/pubmed/36744859
http://dx.doi.org/10.7554/eLife.80809
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