Involvement of Kindlin-1 in cutaneous squamous cell carcinoma.
Journal
Oncogenesis
ISSN: 2157-9024
Titre abrégé: Oncogenesis
Pays: United States
ID NLM: 101580004
Informations de publication
Date de publication:
09 Jul 2024
09 Jul 2024
Historique:
received:
26
12
2023
accepted:
01
07
2024
revised:
19
06
2024
medline:
10
7
2024
pubmed:
10
7
2024
entrez:
9
7
2024
Statut:
epublish
Résumé
Kindler syndrome (KS) is a rare genodermatosis resulting from loss-of-function mutations in FERMT1, the gene that encodes Kindlin-1. KS patients have a high propensity to develop aggressive and metastatic cutaneous squamous cell carcinoma (cSCC). Here we show in non-KS-associated patients that elevation of FERMT1 expression is increased in actinic keratoses compared to normal skin, with a further increase in cSCC supporting a pro-tumorigenic role in this population. In contrast, we show that loss of Kindlin-1 leads to increased SCC tumor growth in vivo and in 3D spheroids, which was associated with the development of a hypoxic tumor environment and increased glycolysis. The metalloproteinase Mmp13 was upregulated in Kindlin-1-depleted tumors, and increased expression of MMP13 was responsible for driving increased invasion of the Kindlin-1-depleted SCC cells. These results provide evidence that Kindlin-1 loss in SCC can promote invasion through the upregulation of MMP13, and offer novel insights into how Kindlin-1 loss leads to the development of a hypoxic environment that is permissive for tumor growth.
Identifiants
pubmed: 38982038
doi: 10.1038/s41389-024-00526-1
pii: 10.1038/s41389-024-00526-1
doi:
Types de publication
Journal Article
Langues
eng
Pagination
24Subventions
Organisme : Dystrophic Epidermolysis Bullosa Research Association (DEBRA)
ID : Brunton 2
Organisme : Dystrophic Epidermolysis Bullosa Research Association (DEBRA)
ID : Brunton 2
Organisme : Cancer Research UK (CRUK)
ID : SEBCATP-2023/100009
Organisme : Cancer Research UK (CRUK)
ID : SEBCATP-2023/100009
Organisme : Cancer Research UK (CRUK)
ID : C157/A24837
Organisme : Cancer Research UK (CRUK)
ID : C157/A29279
Organisme : Cancer Research UK (CRUK)
ID : A31287
Organisme : Cancer Research UK (CRUK)
ID : A29802
Organisme : EC | Horizon 2020 Framework Programme (EU Framework Programme for Research and Innovation H2020)
ID : 801423
Informations de copyright
© 2024. The Author(s).
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