Altered endosomal-lysosomal biogenesis in melanoma

Cutaneous melanoma is the deadliest form of skin neoplasm and its high mortality rates could be averted by early accurate detection. While the detection of melanoma is currently reliant upon melanin visualisation, research into melanosome biogenesis, as a key driver of pathogenesis, has not yielded...

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Published in:Neoplasia (New York, N.Y.) N.Y.), 2023-09, Vol.43, p.100924-100924, Article 100924
Main Authors: Lam, Giang T, Sorvina, Alexandra, Martini, Carmela, Prabhakaran, Sarita, Ung, Ben S-Y, Lazniewska, Joanna, Moore, Courtney R, Beck, Andrew R, Hopkins, Ashley M, Johnson, Ian R D, Caruso, Maria C, Hickey, Shane M, Brooks, Robert D, Jackett, Louise, Karageorgos, Litsa, Foster-Smith, Erwin J, Malone, Victoria, Klebe, Sonja, O'Leary, John J, Brooks, Douglas A, Logan, Jessica M
Format: Article
Language:English
Subjects:
Carcinoma, Squamous Cell - pathology
Endosomal-lysosomal biogenesis
Humans
IGF2R
Lysosomes - genetics
Lysosomes - pathology
Melanoma - pathology
Melanoma pathogenesis
Melanoma, Cutaneous Malignant
Original Research
rab GTP-Binding Proteins
Rab25
Skin Neoplasms - pathology
Sortilin
Syntenin-1
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Summary:Cutaneous melanoma is the deadliest form of skin neoplasm and its high mortality rates could be averted by early accurate detection. While the detection of melanoma is currently reliant upon melanin visualisation, research into melanosome biogenesis, as a key driver of pathogenesis, has not yielded technology that can reliably distinguish between atypical benign, amelanotic and melanotic lesions. The endosomal-lysosomal system has important regulatory roles in cancer cell biology, including a specific functional role in melanosome biogenesis. Herein, the involvement of the endosomal-lysosomal system in melanoma was examined by pooled secondary analysis of existing gene expression datasets. A set of differentially expressed endosomal-lysosomal genes was identified in melanoma, which were interconnected by biological function. To illustrate the protein expression of the dysregulated genes, immunohistochemistry was performed on samples from patients with cutaneous melanoma to reveal candidate markers. This study demonstrated the dysregulation of Syntenin-1, Sortilin and Rab25 may provide a differentiating feature between cutaneous melanoma and squamous cell carcinoma, while IGF2R may indicate malignant propensity in these skin cancers.
ISSN:1476-5586
1522-8002
1476-5586
DOI:10.1016/j.neo.2023.100924