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Wolfstetter, G., Pfeifer, K., Backman, M., Masudi, T.A., Mendoza-García, P., Chen, S., Sonnenberg, H., Sukumar, S.K., Uçkun, E., Varshney, G.K., Uv, A., Palmer, R.H. (2020). Identification of the Wallenda JNKKK as an Alk suppressor reveals increased competitiveness of Alk-expressing cells.  Sci. Rep. 10(1): 14954.
FlyBase ID
FBrf0246671
Publication Type
Research paper
Abstract

Anaplastic lymphoma kinase (Alk) is a receptor tyrosine kinase of the insulin receptor super-family that functions as oncogenic driver in a range of human cancers such as neuroblastoma. In order to investigate mechanisms underlying Alk oncogenic signaling, we conducted a genetic suppressor screen in Drosophila melanogaster. Our screen identified multiple loci important for Alk signaling, including members of Ras/Raf/ERK-, Pi3K-, and STAT-pathways as well as tailless (tll) and foxo whose orthologues NR2E1/TLX and FOXO3 are transcription factors implicated in human neuroblastoma. Many of the identified suppressors were also able to modulate signaling output from activated oncogenic variants of human ALK, suggesting that our screen identified targets likely relevant in a wide range of contexts. Interestingly, two misexpression alleles of wallenda (wnd, encoding a leucine zipper bearing kinase similar to human DLK and LZK) were among the strongest suppressors. We show that Alk expression leads to a growth advantage and induces cell death in surrounding cells. Our results suggest that Alk activity conveys a competitive advantage to cells, which can be reversed by over-expression of the JNK kinase kinase Wnd.

PubMed ID
PubMed Central ID
PMC7486895 (PMC) (EuropePMC)
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    Language of Publication
    English
    Additional Languages of Abstract
    Parent Publication
    Publication Type
    Journal
    Abbreviation
    Sci. Rep.
    Title
    Scientific reports
    ISBN/ISSN
    2045-2322
    Data From Reference
    Aberrations (5)
    Alleles (37)
    Genes (69)
    Human Disease Models (2)
    Natural transposons (1)
    Insertions (6)
    Experimental Tools (3)
    Transgenic Constructs (23)