ArticleCellular oncology (Dordrecht, Netherlands)2019
The X-linked inhibitor of apoptosis protein (XIAP) is involved in melanoma invasion by regulating cell migration and survival.
Article in Cellular oncology (Dordrecht, Netherlands), 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers, 1 of them a synthesis that pooled it.
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Who cites it
8 citing papers in PubMed, 1 synthesis or guideline pooled it, 20 citations in OpenAlex.
- How miRNAs Regulate Schwann Cells during Peripheral Nerve Regeneration-A Systemic Review.International journal of molecular sciences · 2022Pooled it
- Discovery of novel and highly potent XIAP-targeted peptide inhibitors using virtual screening.Journal of enzyme inhibition and medicinal chemistry · 2026Article
- Uncovering the molecular signature of feline diffuse iris melanoma through transcriptomic analysis of disease severity.Scientific reports · 2025Article
- Proteomic Analysis Highlights the Impact of the Sphingolipid Metabolizing Enzyme β-Galactosylceramidase on Mitochondrial Plasticity in Human Melanoma.International journal of molecular sciences · 2024Article
- Loss of miR-101-3p in melanoma stabilizes genomic integrity, leading to cell death prevention.Cellular & molecular biology letters · 2024Article
- MicroRNAs, long non-coding RNAs, and circular RNAs and gynecological cancers: focus on metastasis.Frontiers in oncology · 2023Review
- XIAP promotes melanoma growth by inducing tumour neutrophil infiltration.EMBO reports · 2022Article
- A paradoxical role for sestrin 2 protein in tumor suppression and tumorigenesis.Cancer cell international · 2021Review
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Authors and funding
6 authors at 3 institutions in 1 country.
Funding
Abstract
backgroundThe X-linked inhibitor of apoptosis (XIAP) is a potent cellular inhibitor of apoptosis, based on its unique capability to bind and to inhibit caspases. However, XIAP is also involved in a number of additional cellular activities independent of its caspase inhibitory function. The aim of this study was to investigate whether modulation of XIAP expression affects apoptosis-independent functions of XIAP in melanoma cells, restores their sensitivity to apoptosis and/or affects their invasive and metastatic capacities.
methodsXIAP protein levels were analyzed by immunohistochemical staining of human tissues and by Western blotting of melanoma cell lysates. The effects of pharmacological inhibition or of XIAP down-regulation were investigated using ex-vivo and transwell invasion assays. The biological effects of XIAP down-regulation on melanoma cells were analyzed in vitro using BrdU/PI, nucleosome quantification, adhesion and migration assays. In addition, new XIAP binding partners were identified by co-immunoprecipitation followed by mass spectrometry.
resultsHere we found that the expression of XIAP is increased in metastatic melanomas and in invasive melanoma-derived cell lines. We also found that the bivalent IAP antagonist birinapant significantly reduced the invasive capability of melanoma cells. This reduction could be reproduced by downregulating XIAP in melanoma cells. Furthermore, we found that the migration of melanoma cells and the formation of focal adhesions at cellular borders on fibronectin-coated surfaces were significantly reduced upon XIAP knockdown. This reduction may depend on an altered vimentin-XIAP association, since we identified vimentin as a new binding partner of XIAP. As a corollary of these molecular alterations, we found that XIAP down-regulation in melanoma cells led to a significant decrease in invasion of dermal skin equivalents.
conclusionFrom our data we conclude that XIAP acts as a multifunctional pro-metastatic protein in skin melanomas and, as a consequence, that XIAP may serve as a therapeutic target for these melanomas.
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