WNT signalling in the normal human adult testis and in male germ cell neoplasms.
Abstract
Is WNT signalling functional in normal and/or neoplastic human male germ cells? Regulated WNT signalling component synthesis in human testes indicates that WNT pathway function changes during normal spermatogenesis and is active in testicular germ cell tumours (TGCTs), and that WNT pathway blockade may restrict seminoma growth and migration. Regulated WNT signalling governs many developmental processes, including those affecting male fertility during early germ cell development at embryonic and adult (spermatogonial) ages in mice. In addition, although many cancers arise from WNT signalling alterations, the functional relevance and WNT pathway components in TGCT, including germ cell neoplasia in situ (GCNIS), are unknown. The cellular distribution of transcripts and proteins in WNT signalling pathways was assessed in fixed human testis sections with normal spermatogenesis, GCNIS and seminoma (2-16 individuals per condition). Short-term (1-7 h) ligand activation and long-term (1-5 days) functional outcomes were examined using the well-characterised seminoma cell line, TCam-2. Pathway inhibition used siRNA or chemical exposures over 5 days to assess survival and migration. The cellular localisation of WNT signalling components wa...Continue Reading
References
Wnt signaling promotes proliferation and stemness regulation of spermatogonial stem/progenitor cells
Inhibition of tankyrases induces Axin stabilization and blocks Wnt signalling in breast cancer cells
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