The RBP1-CKAP4 axis activates oncogenic autophagy and promotes cancer progression in oral squamous cell carcinoma.
Animals
Autophagy
Autophagy-Related Protein 5
/ metabolism
Carcinogenesis
/ metabolism
Carcinoma, Squamous Cell
/ genetics
Cell Line, Tumor
Cell Movement
/ genetics
Cell Proliferation
/ genetics
Disease Progression
Down-Regulation
/ genetics
Gene Expression Regulation, Neoplastic
Humans
Membrane Proteins
/ metabolism
Mice, Inbred BALB C
Mice, Nude
Mouth Neoplasms
/ genetics
Neoplasm Invasiveness
Protein Binding
Retinol-Binding Proteins, Cellular
/ metabolism
Signal Transduction
Vacuoles
/ metabolism
Journal
Cell death & disease
ISSN: 2041-4889
Titre abrégé: Cell Death Dis
Pays: England
ID NLM: 101524092
Informations de publication
Date de publication:
25 06 2020
25 06 2020
Historique:
received:
06
11
2019
accepted:
15
06
2020
revised:
11
06
2020
entrez:
27
6
2020
pubmed:
27
6
2020
medline:
19
3
2021
Statut:
epublish
Résumé
Retinol-binding protein 1 (RBP1) is involved in several physiological functions, including the regulation of the metabolism and retinol transport. Studies have shown that it plays an important role in the pathogenesis of several types of cancer. However, the role of RBP1 and its correlation with autophagy in oral squamous cell carcinoma (OSCC) pathogenesis remain unknown. In this study, RBP1 was identified as the most significantly upregulated DEPs with a >2-fold change in OSCC samples when compared to normal tissues through iTRAQ-based proteomics analysis coupled with 2D LC-MS/MS. RBP1 overexpression was significantly associated with malignant phenotypes (differentiation, TNM stage, and lymphatic metastasis) of OSCC. In vitro experiments demonstrated that RBP1 was significantly increased in OSCC tissues and cell lines compared with control group. RBP1 overexpression promoted cell growth, migration, and invasion of OSCC cells. Silencing of RBP1 suppressed tumor formation in xenografted mice. We further demonstrated that the RBP1-CKAP4 axis was a critical regulator of the autophagic machinery in OSCC, inactivation of autophagy rescued the RBP1-CKAP4-mediated malignant biological behaviors of OSCC cells. Overall, a mechanistic link was provided by RBP1-CKAP4 between primary oncogenic features and the induction of autophagy, which may provide a potential therapeutic target that warrants further investigation for treatment of OSCC.
Identifiants
pubmed: 32587255
doi: 10.1038/s41419-020-2693-8
pii: 10.1038/s41419-020-2693-8
pmc: PMC7316825
doi:
Substances chimiques
Autophagy-Related Protein 5
0
CKAP4 protein, human
0
Membrane Proteins
0
Retinol-Binding Proteins, Cellular
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
488Références
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