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

Publication ,  Journal Article
Badarinath, K; Dam, B; Kataria, S; Zirmire, RK; Dey, R; Kansagara, G; Ajnabi, J; Hegde, A; Singh, R; Masudi, T; Sambath, J; Sachithanandan, SP ...
Published in: Cell Rep
September 20, 2022

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.

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Published In

Cell Rep

DOI

EISSN

2211-1247

Publication Date

September 20, 2022

Volume

40

Issue

12

Start / End Page

111390

Location

United States

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

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Badarinath, K., Dam, B., Kataria, S., Zirmire, R. K., Dey, R., Kansagara, G., … Jamora, C. (2022). Snail maintains the stem/progenitor state of skin epithelial cells and carcinomas through the autocrine effect of matricellular protein Mindin. Cell Rep, 40(12), 111390. https://doi.org/10.1016/j.celrep.2022.111390
Badarinath, Krithika, Binita Dam, Sunny Kataria, Ravindra K. Zirmire, Rakesh Dey, Gaurav Kansagara, Johan Ajnabi, et al. “Snail maintains the stem/progenitor state of skin epithelial cells and carcinomas through the autocrine effect of matricellular protein Mindin.Cell Rep 40, no. 12 (September 20, 2022): 111390. https://doi.org/10.1016/j.celrep.2022.111390.
Badarinath K, Dam B, Kataria S, Zirmire RK, Dey R, Kansagara G, et al. 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.
Badarinath, Krithika, et al. “Snail maintains the stem/progenitor state of skin epithelial cells and carcinomas through the autocrine effect of matricellular protein Mindin.Cell Rep, vol. 40, no. 12, Sept. 2022, p. 111390. Pubmed, doi:10.1016/j.celrep.2022.111390.
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. 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.
Journal cover image

Published In

Cell Rep

DOI

EISSN

2211-1247

Publication Date

September 20, 2022

Volume

40

Issue

12

Start / End Page

111390

Location

United States

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