Serine/threonine-protein kinase D2-mediated phosphorylation of DSG2 threonine 730 promotes esophageal squamous cell carcinoma progression.
DSG2
PRKD2
esophageal squamous cell carcinoma
migration and invasion
phosphorylation
Journal
The Journal of pathology
ISSN: 1096-9896
Titre abrégé: J Pathol
Pays: England
ID NLM: 0204634
Informations de publication
Date de publication:
27 Feb 2024
27 Feb 2024
Historique:
revised:
23
12
2023
received:
30
04
2023
accepted:
16
01
2024
medline:
27
2
2024
pubmed:
27
2
2024
entrez:
27
2
2024
Statut:
aheadofprint
Résumé
Desmoglein-2 (DSG2) is a transmembrane glycoprotein belonging to the desmosomal cadherin family, which mediates cell-cell junctions; regulates cell proliferation, migration, and invasion; and promotes tumor development and metastasis. We previously showed serum DSG2 to be a potential biomarker for the diagnosis of esophageal squamous cell carcinoma (ESCC), although the significance and underlying molecular mechanisms were not identified. Here, we found that DSG2 was increased in ESCC tissues compared with adjacent tissues. In addition, we demonstrated that DSG2 promoted ESCC cell migration and invasion. Furthermore, using interactome analysis, we identified serine/threonine-protein kinase D2 (PRKD2) as a novel DSG2 kinase that mediates the phosphorylation of DSG2 at threonine 730 (T730). Functionally, DSG2 promoted ESCC cell migration and invasion dependent on DSG2-T730 phosphorylation. Mechanistically, DSG2 T730 phosphorylation activated EGFR, Src, AKT, and ERK signaling pathways. In addition, DSG2 and PRKD2 were positively correlated with each other, and the overall survival time of ESCC patients with high DSG2 and PRKD2 was shorter than that of patients with low DSG2 and PRKD2 levels. In summary, PRKD2 is a novel DSG2 kinase, and PRKD2-mediated DSG2 T730 phosphorylation promotes ESCC progression. These findings may facilitate the development of future therapeutic agents that target DSG2 and DSG2 phosphorylation. © 2024 The Pathological Society of Great Britain and Ireland.
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : National Natural Science Foundation of China
ID : 81773138
Organisme : Department of Education of Guangdong Province
ID : 2021KCXTD005
Organisme : The Natural Science Foundation of Guangdong Province-Outstanding Youth Project
ID : 2019B151502059
Informations de copyright
© 2024 The Pathological Society of Great Britain and Ireland.
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