Melanoma cells repress Desmoglein 1 in keratinocytes to promote tumor cell migration

Hope E. Burks, Jenny L. Pokorny, Jennifer L. Koetsier, Quinn R. Roth-Carter, Christopher R. Arnette, Pedram Gerami, John T. Seykora, Jodi L. Johnson, Ziyou Ren, Kathleen J. Green*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

10 Scopus citations

Abstract

Melanoma is an aggressive cancer typically arising from transformation of melanocytes residing in the basal layer of the epidermis, where they are in direct contact with surrounding keratinocytes. The role of keratinocytes in shaping the melanoma tumor microenvironment remains understudied. We previously showed that temporary loss of the keratinocyte-specific cadherin, Desmoglein 1 (Dsg1), controls paracrine signaling between normal melanocytes and keratinocytes to stimulate the protective tanning response. Here, we provide evidence that melanoma cells hijack this intercellular communication by secreting factors that keep Dsg1 expression low in the surrounding keratinocytes, which in turn generate their own paracrine signals that enhance melanoma spread through CXCL1/CXCR2 signaling. Evidence suggests a model whereby paracrine signaling from melanoma cells increases levels of the transcriptional repressor Slug, and consequently decreases expression of the Dsg1 transcriptional activator Grhl1. Together, these data support the idea that paracrine crosstalk between melanoma cells and keratinocytes resulting in chronic keratinocyte Dsg1 reduction contributes to melanoma cell movement associated with tumor progression.

Original languageEnglish (US)
Article numbere202212031
JournalJournal of Cell Biology
Volume222
Issue number11
DOIs
StatePublished - Nov 6 2023

Funding

The research was supported by the National Institutes of Health (NIH)/National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) P30 AR075049 awarded to Northwestern University Skin Biology and Diseases Resource-Based Center. Histology services were provided by the Northwestern University Mouse Histology and Phenotyping Laboratory, which is supported by the National Cancer Institute (NCI) P30-CA060553, awarded to the Robert H. Lurie Comprehensive Cancer Center. This work was supported by NIH/NCI R01 CA228196 with additional support from NIH/NIAMS R01 AR041836, NIH/NIAMS R01 AR043380, and the J.L. Mayberry Endowment to K.J. Green. J.L. Pokorny was supported by NIH/ NCI T32 CA009560. H.E. Burks was supported by NIH/NCI T32 CA080621-14. Q.R. Roth-Carter was supported by NIH/NCI T32 CA070085. J.T. Seykora was supported by NIH/NIAMS P30-AR069589.

Keywords

  • Cancer
  • Cell signaling

ASJC Scopus subject areas

  • Cell Biology

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