The Drosophila functional Smad suppressing element fuss, a homologue of the human Skor genes, retains pro-oncogenic properties of the Ski/Sno family

PLoS One. 2022 Jan 14;17(1):e0262360. doi: 10.1371/journal.pone.0262360. eCollection 2022.

Abstract

Over the years Ski and Sno have been found to be involved in cancer progression e.g. in oesophageal squamous cell carcinoma, melanoma, oestrogen receptor-positive breast carcinoma, colorectal carcinoma, and leukaemia. Often, their prooncogenic features have been linked to their ability of inhibiting the anti-proliferative action of TGF-ß signalling. Recently, not only pro-oncogenic but also anti-oncogenic functions of Ski/Sno proteins have been revealed. Besides Ski and Sno, which are ubiquitously expressed other members of Ski/Sno proteins exist which show highly specific neuronal expression, the SKI Family Transcriptional Corepressors (Skor). Among others Skor1 and Skor2 are involved in the development of Purkinje neurons and a mutation of Skor1 has been found to be associated with restless legs syndrome. But neither Skor1 nor Skor2 have been reported to be involved in cancer progression. Using overexpression studies in the Drosophila eye imaginal disc, we analysed if the Drosophila Skor homologue Fuss has retained the potential to inhibit differentiation and induce increased proliferation. Fuss expressed in cells posterior to the morphogenetic furrow, impairs photoreceptor axon pathfinding and inhibits differentiation of accessory cells. However, if its expression is induced prior to eye differentiation, Fuss might inhibit the differentiating function of Dpp signalling and might maintain proliferative action of Wg signalling, which is reminiscent of the Ski/Sno protein function in cancer.

MeSH terms

  • Acyltransferases / metabolism
  • Animals
  • Cell Differentiation / physiology
  • Cell Proliferation / physiology
  • Drosophila Proteins / metabolism*
  • Drosophila Proteins / physiology
  • Drosophila melanogaster / metabolism
  • Imaginal Discs / metabolism
  • Imaginal Discs / physiology*
  • Intracellular Signaling Peptides and Proteins / metabolism
  • Nerve Tissue Proteins / metabolism*
  • Nerve Tissue Proteins / physiology
  • Nuclear Proteins / genetics
  • Oncogenes / genetics
  • Proto-Oncogene Proteins / metabolism*
  • Proto-Oncogene Proteins / physiology
  • Signal Transduction / physiology
  • Transcription Factors / genetics
  • Transforming Growth Factor beta / metabolism

Substances

  • Drosophila Proteins
  • Intracellular Signaling Peptides and Proteins
  • Nerve Tissue Proteins
  • Nuclear Proteins
  • Proto-Oncogene Proteins
  • Snoo protein, Drosophila
  • Transcription Factors
  • Transforming Growth Factor beta
  • fuss protein, Drosophila
  • rasp protein, Drosophila
  • Acyltransferases

Grants and funding

The author(s) received no specific funding for this work.