IRF2BP2 drives lymphatic metastasis in OSCC cells by elevating mitochondrial fission-dependent fatty acid oxidation.
Humans
Squamous Cell Carcinoma of Head and Neck
/ genetics
Carcinoma, Squamous Cell
/ metabolism
Mouth Neoplasms
/ pathology
Lymphatic Metastasis
Mitochondrial Dynamics
Epithelial-Mesenchymal Transition
Cell Line, Tumor
Head and Neck Neoplasms
Fatty Acids
Cell Movement
DNA-Binding Proteins
Transcription Factors
IRF2BP2
fatty acid oxidation
lymph node metastasis
mitochondrial fission
oral squamous cell carcinoma
Journal
Molecular carcinogenesis
ISSN: 1098-2744
Titre abrégé: Mol Carcinog
Pays: United States
ID NLM: 8811105
Informations de publication
Date de publication:
Jan 2024
Jan 2024
Historique:
revised:
02
09
2023
received:
08
04
2023
accepted:
08
09
2023
medline:
6
12
2023
pubmed:
22
9
2023
entrez:
22
9
2023
Statut:
ppublish
Résumé
Lymph node metastasis (LNM) is a major determinant for the poor outcome of oral squamous cell carcinoma (OSCC). Interferon regulatory factor 2 binding protein 2 (IRF2BP2) has been reported to modulate the development and progression of several types of cancers, while its role in OSCC with LNM has not been reported yet. The expression of IRF2BP2 and its association with LNM were evaluated by immunohistochemistry and qualitative reverse transcription polymerase chain reaction in clinically collected OSCC tissues. Then, loss-of-function and rescue assays were conducted to identify the role of IRF2BP2-mediated fatty acid oxidation (FAO) in the invasion, lymphoinvasion, and epithelial-mesenchymal transition (EMT) in OSCC cells. Importantly, confocal microscope, transmission electron microscope, immunofluorescence, and Western blot were applied to identify the involvement of mitochondrial fission in IRF2BP2-regulated FAO. Lastly, the in vivo models were established to evaluate the role of IRF2BP2 in OSCC. IRF2BP2 overexpression has been associated with LNM in OSCC, whose knockdown inhibited invasion, lymphoinvasion, and EMT of OSCC cells, as well as retarded FAO rate with CPT1A downregulation. And CPT1A overexpression rescued invasion, lymphoinvasion, and induced EMT in IRF2BP2-silenced OSCC cells. Mechanically, IRF2BP2 accelerated mitochondrial fission by contributing to Drp1 S616 phosphorylation and mitochondrial localization, resulting in the upregulation of CPT1A. In addition, IRF2BP2 knockdown significantly inhibited tumor growth and LNM in vivo. The highly expressed IRF2BP2 may induce the phosphorylation and mitochondrial translocation of Drp1 to activate mitochondrial fission, which upregulated CPT1A expression and FAO rate, resulting in LNM in OSCC. This highlighted a potential therapeutic vulnerability for the treatment of LNM
Substances chimiques
Fatty Acids
0
IRF2BP2 protein, human
0
DNA-Binding Proteins
0
Transcription Factors
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
45-60Subventions
Organisme : National Natural Science Foundation of China grants
ID : 82073000
Organisme : National Natural Science Foundation of China grants
ID : 81972542
Organisme : National Natural Science Foundation of China grants
ID : 82173326
Organisme : Exploration and research projects of West China College of Stomatology, Sichuan University
ID : RD-03-202004
Organisme : Science Foundation of Sichuan Province
ID : 2022YFS0289
Organisme : Clinical Project of West China College of Stomatology, Sichuan University
ID : LCYJ2019-8
Informations de copyright
© 2023 Wiley Periodicals LLC.
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