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GLI Transcriptional Targets S100A7 and KRT16 Show Upregulated Expression Patterns in Epidermis Overlying the Tumor Mass in Melanoma Samples.
- Source :
-
International journal of molecular sciences [Int J Mol Sci] 2024 May 31; Vol. 25 (11). Date of Electronic Publication: 2024 May 31. - Publication Year :
- 2024
-
Abstract
- Although not completely understood, the role of the Hedgehog-GLI (HH-GLI) signaling pathway in melanoma and epithelial skin tumors has been reported before. In this study, we confirmed in various melanoma cell line models that keratin 16 (KRT16) and S100 Calcium-Binding Protein A7 (S100A7) are transcriptional targets of GLI Family Zinc Finger (GLI) proteins. Besides their important role in protecting and maintaining the epidermal barrier, keratins are somehow tightly connected with the S100 family of proteins. We found that stronger expression of KRT16 indeed corresponds to stronger expression of S100A7 in our clinical melanoma samples. We also report a trend regarding staining of GLI1, which corresponds to stronger staining of GLI3, KRT16, and S100A7 proteins. The most interesting of our findings is that all the proteins are detected specifically in the epidermis overlying the tumor, but rarely in the tumor itself. The examined proteins were also not detected in the healthy epidermis at the edges of the sample, suggesting that the staining is specific to the epidermis overlaying the tumor mass. Of all proteins, only S100A7 demonstrated a statistically significant trend regarding tumor staging and staining intensity. Results from our clinical samples prove that immune infiltration is an important feature of melanoma. Pigmentophages and tumor-infiltrating lymphocytes (TIL) demonstrate a significant association with tumor stage, while mononuclear cells are equally present in all stages. For S100A7, we found an association between the number of TILs and staining intensity. Considering these new findings presented in our study, we suggest a more detailed examination of the possible role of the S100A7 protein as a biomarker in melanoma.
- Subjects :
- Humans
Cell Line, Tumor
Up-Regulation
Male
Female
Middle Aged
Biomarkers, Tumor metabolism
Biomarkers, Tumor genetics
Aged
Melanoma metabolism
Melanoma pathology
Melanoma genetics
S100 Calcium Binding Protein A7 metabolism
S100 Calcium Binding Protein A7 genetics
Epidermis metabolism
Epidermis pathology
Skin Neoplasms metabolism
Skin Neoplasms pathology
Skin Neoplasms genetics
Gene Expression Regulation, Neoplastic
Zinc Finger Protein GLI1 metabolism
Zinc Finger Protein GLI1 genetics
Keratin-16 metabolism
Keratin-16 genetics
Subjects
Details
- Language :
- English
- ISSN :
- 1422-0067
- Volume :
- 25
- Issue :
- 11
- Database :
- MEDLINE
- Journal :
- International journal of molecular sciences
- Publication Type :
- Academic Journal
- Accession number :
- 38892279
- Full Text :
- https://doi.org/10.3390/ijms25116084