Snail maintains the stem/progenitor state of skin epithelial cells and carcinomas through the autocrine effect of matricellular protein Mindin.
Preservation of a small population of cancer stem cells (CSCs) within a heterogeneous carcinoma serves as a paradigm to understand how select cells in a tissue maintain their undifferentiated status. In both embryogenesis and cancer, Snail has been correlated with stemness, but the molecular underpinning of this phenomenon remains largely ill-defined. In models of cutaneous squamous cell carcinoma (cSCC), we discovered a non-epithelial-mesenchymal transition function for the transcription factor Snail in maintaining the stemness of epidermal keratinocytes. Snail-expressing cells secrete the matricellular protein Mindin, which functions in an autocrine fashion to activate a Src-STAT3 pathway to reinforce their stem/progenitor phenotype. This pathway is activated by the engagement of Mindin with the leukocyte-specific integrin, CD11b (ITGAM), which is also unexpectedly expressed by epidermal keratinocytes. Interestingly, disruption of this signaling module in human cSCC attenuates tumorigenesis, suggesting that targeting Mindin would be a promising therapeutic approach to hinder cancer recurrence.
Duke Scholars
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Related Subject Headings
- Snail Family Transcription Factors
- Skin Neoplasms
- Neoplastic Stem Cells
- Neoplasm Recurrence, Local
- Neoplasm Proteins
- Integrins
- Humans
- Extracellular Matrix Proteins
- Epithelial Cells
- Cell Line, Tumor
Citation
Published In
DOI
EISSN
Publication Date
Volume
Issue
Start / End Page
Location
Related Subject Headings
- Snail Family Transcription Factors
- Skin Neoplasms
- Neoplastic Stem Cells
- Neoplasm Recurrence, Local
- Neoplasm Proteins
- Integrins
- Humans
- Extracellular Matrix Proteins
- Epithelial Cells
- Cell Line, Tumor