ABCC1 Is a ΔNp63 Target Gene Overexpressed in Squamous Cell Carcinoma.

Autor: La Banca V; Department of Experimental Medicine, University of Rome 'Tor Vergata', Via Montpellier 1, 00133 Rome, Italy., De Domenico S; Department of Experimental Medicine, University of Rome 'Tor Vergata', Via Montpellier 1, 00133 Rome, Italy., Nicolai S; Institute of Translational Pharmacology (IFT), CNR, Via Fosso del Cavaliere 100, 00133 Rome, Italy., Gatti V; Institute of Translational Pharmacology (IFT), CNR, Via Fosso del Cavaliere 100, 00133 Rome, Italy., Scalera S; UOSD Clinical Trial Center, Biostatistics and Bioinformatics Division, IRCCS Regina Elena National Cancer Institute, 00144 Rome, Italy., Maugeri M; UOSD Clinical Trial Center, Biostatistics and Bioinformatics Division, IRCCS Regina Elena National Cancer Institute, 00144 Rome, Italy., Mauriello A; Department of Experimental Medicine, University of Rome 'Tor Vergata', Via Montpellier 1, 00133 Rome, Italy., Montanaro M; Department of Biomedicine and Prevention, University of Rome 'Tor Vergata', Via Montpellier 1, 00133 Rome, Italy., Pahnke J; Translational Neurodegeneration Research and Neuropathology Lab/Section of Neuropathology Research, Department of Pathology (PAT), Medical Faculty/Clinical Medicine (KlinMed), Clinics for Laboratory Medicine (KLM), University of Oslo (UiO) and Oslo University Hospital (OUS), Sognsvannsveien 20, 0372 Oslo, Norway.; Institute of Nutritional Medicine (INUM)/Lübeck Institute of Dermatology (LIED), University of Lübeck (UzL) and University Medical Center Schleswig-Holstein (UKSH), Ratzeburger Allee 160, D-23538 Lübeck, Germany.; Department of Pharmacology, The Faculty of Medicine and Life Sciences, University of Latvia (LU), Jelgavas iela 3, LV-1004 Rīga, Latvia.; Department of Neurobiology, School of Neurobiology, Biochemistry and Biophysics, The Georg S. Wise Faculty of Life Sciences, Tel Aviv University (TAU), Tel Aviv 6997801, Israel., Candi E; Department of Experimental Medicine, University of Rome 'Tor Vergata', Via Montpellier 1, 00133 Rome, Italy.; Biochemistry Laboratory, Istituto Dermopatico Immacolata (IDI-IRCCS), 00166 Rome, Italy., D'Amico S; Institute of Translational Pharmacology (IFT), CNR, Via Fosso del Cavaliere 100, 00133 Rome, Italy., Peschiaroli A; Institute of Translational Pharmacology (IFT), CNR, Via Fosso del Cavaliere 100, 00133 Rome, Italy.
Jazyk: angličtina
Zdroj: International journal of molecular sciences [Int J Mol Sci] 2024 Aug 10; Vol. 25 (16). Date of Electronic Publication: 2024 Aug 10.
DOI: 10.3390/ijms25168741
Abstrakt: 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.
Databáze: MEDLINE
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