TMTC1 promotes invasiveness of ovarian cancer cells through integrins β1 and β4.
Journal
Cancer gene therapy
ISSN: 1476-5500
Titre abrégé: Cancer Gene Ther
Pays: England
ID NLM: 9432230
Informations de publication
Date de publication:
08 2023
08 2023
Historique:
received:
17
01
2023
accepted:
04
05
2023
revised:
20
04
2023
medline:
16
8
2023
pubmed:
24
5
2023
entrez:
23
5
2023
Statut:
ppublish
Résumé
Ovarian cancer is the most lethal gynecological malignancy and is characterized by peritoneal disseminated metastasis. Although O-mannosyltransferase TMTC1 is highly expressed by ovarian cancer, its pathophysiological role in ovarian cancer remains unclear. Here, immunohistochemistry showed that TMTC1 was overexpressed in ovarian cancer tissues compared with adjacent normal ovarian tissues, and high TMTC1 expression was associated with poor prognosis in patients with ovarian cancer. Silencing TMTC1 reduced ovarian cancer cell viability, migration, and invasion in vitro, as well as suppressed peritoneal tumor growth and metastasis in vivo. Moreover, TMTC1 knockdown reduced cell-laminin adhesion, which was associated with the decreased phosphorylation of FAK at pY397. Conversely, TMTC1 overexpression promoted these malignant properties in ovarian cancer cells. Glycoproteomic analysis and Concanavalin A (ConA) pull-down assays showed that integrins β1 and β4 were novel O-mannosylated protein substrates of TMTC1. Furthermore, TMTC1-mediated cell migration and invasion were significantly reversed by siRNA-mediated knockdown of integrin β1 or β4. Collectively, these results suggest that TMTC1-mediated invasive behaviors are primarily through integrins β1 and β4 and that TMTC1 is a potential therapeutic target for ovarian cancer.
Identifiants
pubmed: 37221403
doi: 10.1038/s41417-023-00625-y
pii: 10.1038/s41417-023-00625-y
pmc: PMC10425284
doi:
Substances chimiques
Carrier Proteins
0
Integrin beta1
0
Membrane Proteins
0
TMTC1 protein, human
0
Integrin beta4
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1134-1143Informations de copyright
© 2023. The Author(s).
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