We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- Title
ABCC1 Is a ΔNp63 Target Gene Overexpressed in Squamous Cell Carcinoma.
- Authors
La Banca, Veronica; De Domenico, Sara; Nicolai, Sara; Gatti, Veronica; Scalera, Stefano; Maugeri, Marcello; Mauriello, Alessandro; Montanaro, Manuela; Pahnke, Jens; Candi, Eleonora; D'Amico, Silvia; Peschiaroli, Angelo
- Abstract
The transcription factor ΔNp63 plays a pivotal role in maintaining the integrity of stratified epithelial tissues by regulating the expression of distinct target genes involved in lineage specification, cell stemness, cell proliferation and differentiation. Here, we identified the ABC transporter subfamily member ABCC1 as a novel ΔNp63 target gene. We found that in immortalized human keratinocytes and in squamous cell carcinoma (SCC) cells, ∆Np63 induces the expression of ABCC1 by physically occupying a p63-binding site (p63 BS) located in the first intron of the ABCC1 gene locus. In cutaneous SCC and during the activation of the keratinocyte differentiation program, ∆Np63 and ABCC1 levels are positively correlated raising the possibility that ABCC1 might be involved in the regulation of the proliferative/differentiative capabilities of squamous tissue. However, we did not find any gross alteration in the structure and morphology of the epidermis in humanized hABCC1 knock-out mice. Conversely, we found that the genetic ablation of ABCC1 led to a marked reduction in inflammation-mediated proliferation of keratinocytes, suggesting that ABCC1 might be involved in the regulation of keratinocyte proliferation upon inflammatory/proliferative signals. In line with these observations, we found a significant increase in ABCC1 expression in squamous cell carcinomas (SCCs), a tumor type characterized by keratinocyte hyper-proliferation and a pro-inflammatory tumor microenvironment. Collectively, these data uncover ABCC1 as an additional ∆Np63 target gene potentially involved in those skin diseases characterized by dysregulation of proliferation/differentiation balance.
- Subjects
TRANSCRIPTION factors; GENE expression; KNOCKOUT mice; SQUAMOUS cell carcinoma; ATP-binding cassette transporters; KERATINOCYTE differentiation
- Publication
International Journal of Molecular Sciences, 2024, Vol 25, Issue 16, p8741
- ISSN
1661-6596
- Publication type
Article
- DOI
10.3390/ijms25168741