Snail maintains the stem/progenitor state of skin epithelial cells and carcinomas through the autocrine effect of matricellular protein Mindin

Cell Rep. 2022 Sep 20;40(12):111390. doi: 10.1016/j.celrep.2022.111390.


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.

Keywords: CP: Cancer; CP: Developmental biology; Cancer stem cells; EMT; Mindin; SFK; STAT3; Snail; Tumor heterogeneity; carcinoma; skin cancer.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, N.I.H., Extramural

MeSH terms

  • Carcinoma, Squamous Cell* / pathology
  • Cell Line, Tumor
  • Epithelial Cells / metabolism
  • Extracellular Matrix Proteins
  • Humans
  • Integrins / metabolism
  • Neoplasm Proteins
  • Neoplasm Recurrence, Local / pathology
  • Neoplastic Stem Cells / metabolism
  • Skin Neoplasms* / pathology
  • Snail Family Transcription Factors / metabolism


  • Extracellular Matrix Proteins
  • Integrins
  • Neoplasm Proteins
  • SNAI1 protein, human
  • SPON2 protein, human
  • Snail Family Transcription Factors