Snail maintains the stem/progenitor state of skin epithelial cells and carcinomas through the autocrine effect of matricellular protein Mindin.
|Snail maintains the stem/progenitor state of skin epithelial cells and carcinomas through the autocrine effect of matricellular protein Mindin.
|Year of Publication
|Badarinath K, Dam B, Kataria S, Zirmire RK, Dey R, Kansagara G, Ajnabi J, Hegde A, Singh R, Masudi T, Sambath J, Sachithanandan SP, Kumar P, Gulyani A, He Y-W, Krishna S, Jamora C
|2022 09 20
|Carcinoma, Squamous Cell, Cell Line, Tumor, Epithelial Cells, Extracellular Matrix Proteins, Humans, Integrins, Neoplasm Proteins, Neoplasm Recurrence, Local, Neoplastic Stem Cells, Skin Neoplasms, Snail Family Transcription Factors
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.
|R01 AR053185 / AR / NIAMS NIH HHS / United States