Zinc as a Biomarker of Nutritional Status and Clinical Burden in Recessive Dystrophic Epidermolysis Bullosa: Implications for Preventive Monitoring
Gennaio 12 2026
Inaugurazione della Casa di Camilla
Febbraio 20 2026Mol Biol Cell. 2026 Jan 15:mbcE25040181. doi: 10.1091/mbc.E25-04-0181. Epub ahead of print. PMID: 41537741.
Epithelial-Dermal Inflammasome Crosstalk in Cutaneous Squamous Cell Carcinoma
Authors: Ruochong Wang 1, Kush R Patel 1 2, Raphael R Shu 1 3, Khushi Tekale 1 4, Michael Hamersky 1, Adelaida B Perez 1, David Solano 1, Nooreen Syed 1, Connor E Stewart 1, Joseph Lee 1 5, Allison M Hanlon 6 7, Travis W Blalock 8, Chaoran Li 8 9 10, Lindsey Seldin 1 8 10 11
Affiliation:
- Department of Cell Biology, Emory University School of Medicine, Atlanta, GA, USA.
- Current address: University of Miami School of Medicine, Miami, FL, USA.
- Current address: California Institute of Technology, Pasadena, CA, USA.
- Current address: Rosalind Franklin University of Medicine and Science, North Chicago, IL, USA.
- Current address: University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
- Department of Dermatology, Vanderbilt University Medical Center, Nashville, TN, USA.
- VA Tennessee Valley Healthcare System, Nashville, TN, USA.
- Department of Dermatology, Emory University School of Medicine, Atlanta, GA, USA.
- Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, GA, USA.0Winship Cancer Institute, Emory University School of Medicine, Atlanta, GA, USA.
- Atlanta Veterans Affairs Medical Center, Decatur, GA, USA.
Abstract:
Epithelia maintain their barrier function through the proliferative and plastic behavior of stem cells that drive continuous tissue regeneration. However, these same properties render epithelia susceptible to tumorigenesis. The skin, the largest epithelial barrier, is the source of the most prevalent human cancers, yet the molecular mechanisms by which stem cells and their microenvironment cooperate to promote cutaneous cancer development remain incompletely defined. Prior work demonstrated that genotoxic injury in normal skin activates epithelial-dermal inflammasome signaling that drives epithelial stem cell hyperproliferation and misspecification. Here, we investigated whether this mechanism also operates in diseased skin. We found that stem cell misspecification is a broadly conserved feature across pathological skin conditions but is absent in normally proliferating tissue. Notably, inflammasome activation is detected in both epithelial and dermal compartments of cutaneous squamous cell carcinoma (cSCC), but not in other skin pathologies. Mechanistically, oncogenic KRAS expression in keratinocytes triggers inflammasome activation prior to tumor formation non-cell autonomously. Furthermore, IL-1 signaling is activated in fibroblasts adjacent to the cSCC tumor interface, but not in the overlying epithelium. Taken together, these findings support a model in which KRAS-driven epithelial-fibroblast inflammasome crosstalk establishes a feed-forward IL-1 signaling loop that enhances the tumor-promoting microenvironment in cSCC.