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.
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6 November 2023
Article|
September 21 2023
Melanoma cells repress Desmoglein 1 in keratinocytes to promote tumor cell migration
Hope E. Burks
,
Hope E. Burks
(Conceptualization, Data curation, Formal analysis, Investigation, Methodology, Resources, Visualization, Writing - original draft, Writing - review & editing)
1Department of Pathology, Feinberg School of Medicine,
Northwestern University
, Chicago, IL, USA
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Jenny L. Pokorny
,
Jenny L. Pokorny
(Investigation, Writing - review & editing)
1Department of Pathology, Feinberg School of Medicine,
Northwestern University
, Chicago, IL, USA
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Jennifer L. Koetsier
,
Jennifer L. Koetsier
(Investigation, Methodology, Writing - review & editing)
1Department of Pathology, Feinberg School of Medicine,
Northwestern University
, Chicago, IL, USA
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Quinn R. Roth-Carter
,
Quinn R. Roth-Carter
(Software, Writing - review & editing)
1Department of Pathology, Feinberg School of Medicine,
Northwestern University
, Chicago, IL, USA
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Christopher R. Arnette
,
Christopher R. Arnette
(Resources, Writing - review & editing)
1Department of Pathology, Feinberg School of Medicine,
Northwestern University
, Chicago, IL, USA
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Pedram Gerami
,
Pedram Gerami
(Writing - original draft, Writing - review & editing)
1Department of Pathology, Feinberg School of Medicine,
Northwestern University
, Chicago, IL, USA
2Department of Dermatology, Feinberg School of Medicine,
Northwestern University
, Chicago, IL, USA
3Robert H. Lurie Comprehensive Cancer Center,
Northwestern University
, Chicago, IL, USA
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John T. Seykora
,
John T. Seykora
(Conceptualization, Resources, Supervision, Writing - review & editing)
4Department of Dermatology,
Perelman School of Medicine at the University of Pennsylvania
, Philadelphia, PA, USA
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Jodi L. Johnson
,
Jodi L. Johnson
(Conceptualization, Writing - original draft, Writing - review & editing)
1Department of Pathology, Feinberg School of Medicine,
Northwestern University
, Chicago, IL, USA
2Department of Dermatology, Feinberg School of Medicine,
Northwestern University
, Chicago, IL, USA
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Ziyou Ren
,
Ziyou Ren
(Data curation, Resources, Software)
1Department of Pathology, Feinberg School of Medicine,
Northwestern University
, Chicago, IL, USA
2Department of Dermatology, Feinberg School of Medicine,
Northwestern University
, Chicago, IL, USA
3Robert H. Lurie Comprehensive Cancer Center,
Northwestern University
, Chicago, IL, USA
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Kathleen J. Green
(Conceptualization, Funding acquisition, Project administration, Resources, Supervision, Writing - review & editing)
1Department of Pathology, Feinberg School of Medicine,
Northwestern University
, Chicago, IL, USA
2Department of Dermatology, Feinberg School of Medicine,
Northwestern University
, Chicago, IL, USA
3Robert H. Lurie Comprehensive Cancer Center,
Northwestern University
, Chicago, IL, USA
Correspondence to Kathleen J. Green: kgreen@northwestern.edu
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Hope E. Burks
Conceptualization, Data curation, Formal analysis, Investigation, Methodology, Resources, Visualization, Writing - original draft, Writing - review & editing
1Department of Pathology, Feinberg School of Medicine,
Northwestern University
, Chicago, IL, USA
Jenny L. Pokorny
Investigation, Writing - review & editing
1Department of Pathology, Feinberg School of Medicine,
Northwestern University
, Chicago, IL, USA
Jennifer L. Koetsier
Investigation, Methodology, Writing - review & editing
1Department of Pathology, Feinberg School of Medicine,
Northwestern University
, Chicago, IL, USA
Quinn R. Roth-Carter
Software, Writing - review & editing
1Department of Pathology, Feinberg School of Medicine,
Northwestern University
, Chicago, IL, USA
Christopher R. Arnette
Resources, Writing - review & editing
1Department of Pathology, Feinberg School of Medicine,
Northwestern University
, Chicago, IL, USA
Pedram Gerami
Writing - original draft, Writing - review & editing
1Department of Pathology, Feinberg School of Medicine,
Northwestern University
, Chicago, IL, USA
2Department of Dermatology, Feinberg School of Medicine,
Northwestern University
, Chicago, IL, USA
3Robert H. Lurie Comprehensive Cancer Center,
Northwestern University
, Chicago, IL, USA
John T. Seykora
Conceptualization, Resources, Supervision, Writing - review & editing
4Department of Dermatology,
Perelman School of Medicine at the University of Pennsylvania
, Philadelphia, PA, USA
Jodi L. Johnson
Conceptualization, Writing - original draft, Writing - review & editing
1Department of Pathology, Feinberg School of Medicine,
Northwestern University
, Chicago, IL, USA
2Department of Dermatology, Feinberg School of Medicine,
Northwestern University
, Chicago, IL, USA
Ziyou Ren
Data curation, Resources, Software
1Department of Pathology, Feinberg School of Medicine,
Northwestern University
, Chicago, IL, USA
2Department of Dermatology, Feinberg School of Medicine,
Northwestern University
, Chicago, IL, USA
3Robert H. Lurie Comprehensive Cancer Center,
Northwestern University
, Chicago, IL, USA
Kathleen J. Green
Conceptualization, Funding acquisition, Project administration, Resources, Supervision, Writing - review & editing
1Department of Pathology, Feinberg School of Medicine,
Northwestern University
, Chicago, IL, USA
2Department of Dermatology, Feinberg School of Medicine,
Northwestern University
, Chicago, IL, USA
3Robert H. Lurie Comprehensive Cancer Center,
Northwestern University
, Chicago, IL, USA
Correspondence to Kathleen J. Green: kgreen@northwestern.edu
Disclosures: All authors have completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. P. Gerami reported personal fees from Castle Biosciences outside the submitted work. No other disclosures were reported.
Received:
December 09 2022
Revision Received:
April 25 2023
Accepted:
August 16 2023
Online ISSN: 1540-8140
Print ISSN: 0021-9525
Funding
Funder(s):
National Institutes of Health
- Award Id(s): P30 AR075049,R01 CA228196,R01 AR041836,R01 AR043380,T32 CA009560,T32 CA080621-14,T32 CA070085,P30-AR069589
Funder(s):
National Institute of Arthritis and Musculoskeletal and Skin Diseases
Funder(s):
Northwestern University Mouse Histology
Funder(s):
Phenotyping Laboratory
Funder(s):
National Cancer Institute
- Award Id(s): P30-CA0605
Funder(s):
Robert H. Lurie Comprehensive Cancer Center
© 2023 Burks et al.
2023
Burks et al.
This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms/). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 International license, as described at https://creativecommons.org/licenses/by-nc-sa/4.0/).
J Cell Biol (2023) 222 (11): e202212031.
Article history
Received:
December 09 2022
Revision Received:
April 25 2023
Accepted:
August 16 2023
Citation
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; Melanoma cells repress Desmoglein 1 in keratinocytes to promote tumor cell migration. J Cell Biol 6 November 2023; 222 (11): e202212031. doi: https://doi.org/10.1083/jcb.202212031
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