Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C1522102 (Melanoma)
 7,698 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The epidermis is the first line of defense against ultraviolet (UV) light from the sun. Keratinocytes and melanocytes respond to UV exposure by eliciting a tanning response dependent in part on paracrine signaling, but how keratinocyte:melanocyte communication is regulated during this response remains understudied. Here, we uncover a surprising new function for the keratinocyte-specific cell-cell adhesion molecule desmoglein 1 (Dsg1) in regulating keratinocyte:melanocyte paracrine signaling to promote the tanning response in the absence of UV exposure. Melanocytes within Dsg1-silenced human skin equivalents exhibited increased pigmentation and altered dendrite morphology, phenotypes which were confirmed in 2D culture using conditioned media from Dsg1-silenced keratinocytes. Dsg1-silenced keratinocytes increased melanocyte-stimulating hormone precursor (Pomc) and cytokine mRNA. Melanocytes cultured in media conditioned by Dsg1-silenced keratinocytes increased Mitf and Tyrp1 mRNA, TYRP1 protein, and melanin production and secretion. Melanocytes in Dsg1-silenced skin equivalents mislocalized suprabasally, reminiscent of early melanoma pagetoid behavior. Together with our previous report that UV reduces Dsg1 expression, these data support a role for Dsg1 in controlling keratinocyte:melanocyte paracrine communication and raise the possibility that a Dsg1-deficient niche contributes to pagetoid behavior, such as occurs in early melanoma development.
Pigment Cell Melanoma Res 2020 03
PMID:Keratinocyte cadherin desmoglein 1 controls melanocyte behavior through paracrine signaling. 3156 53

In the animal kingdom, skin pigmentation is highly variable between species and contributes to phenotype. In humans, the role of skin pigmentation is associated with sun protection. Skin pigmentation depends on the ratio of two pigments, pheomelanin and eumelanin, which are synthetized by a specialized cell population, the melanocytes. In this review, we focused on one factor in pigmentation: the tyrosinase-related protein 1 (TYRP1) gene involved in the eumelanin synthesis via TYRP1 protein. Counterintuitively, high TYRP1 mRNA expression is associated with a poor clinical outcome for patients with metastatic melanoma. Recently, we explained this unexpected function of TYRP1 by demonstrating that TYRP1 mRNA sequesters microRNA (miRNA)-16, a tumour suppressor miRNA. Here, we focused on actors influencing TYRP1 mRNA abundance, particularly transcription factors, single nucleotide polymorphisms (SNPs) and miRNAs since they dictate the indirect oncogenic activity of TYRP1.
Pigment Cell Melanoma Res 2020 Dec 11
PMID:Human TYRP1: two functions for a single gene? 3330 5