TitleSnail maintains the stem/progenitor state of skin epithelial cells and carcinomas through the autocrine effect of matricellular protein Mindin.
Publication TypeJournal Article
Year of Publication2022
AuthorsBadarinath 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
JournalCell Rep
Volume40
Issue12
Pagination111390
Date Published2022 09 20
ISSN2211-1247
KeywordsCarcinoma, 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
Abstract

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.
DOI10.1016/j.celrep.2022.111390
Alternate JournalCell Rep
PubMed ID36130502
Grant ListR01 AR053185 / AR / NIAMS NIH HHS / United States

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