Altered endosomal-lysosomal biogenesis in melanoma

Neoplasia. 2023 Sep:43:100924. doi: 10.1016/j.neo.2023.100924. Epub 2023 Aug 9.


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.

Keywords: Endosomal-lysosomal biogenesis; IGF2R; Melanoma pathogenesis; Rab25; Sortilin; Syntenin-1.

MeSH terms

  • Carcinoma, Squamous Cell* / pathology
  • Humans
  • Lysosomes / genetics
  • Lysosomes / pathology
  • Melanoma* / pathology
  • Melanoma, Cutaneous Malignant
  • Skin Neoplasms* / pathology
  • rab GTP-Binding Proteins


  • Rab25 protein, human
  • rab GTP-Binding Proteins