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

Journal Article (Journal Article)

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.

Full Text

Duke Authors

Cited Authors

  • 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

Published Date

  • September 20, 2022

Published In

Volume / Issue

  • 40 / 12

Start / End Page

  • 111390 -

PubMed ID

  • 36130502

Electronic International Standard Serial Number (EISSN)

  • 2211-1247

Digital Object Identifier (DOI)

  • 10.1016/j.celrep.2022.111390


  • eng

Conference Location

  • United States