The RBP1–CKAP4 axis activates oncogenic autophagy and promotes cancer progression in oral squamous cell carcinoma

• Published in: Cell death & disease 2020-06, Vol.11 (6), p.488, Article 488
• Main Authors: Gao, Ling, Wang, Qibo, Ren, Wenhao, Zheng, Jingjing, Li, Shaoming, Dou, Zhichao, Kong, Xinjuan, Liang, Xiao, Zhi, Keqian
• Format: Article
• Language: English
• Subjects: 101/28; 101/58; 13/1; 13/105; 13/31; 13/89; 38/22; 38/77; 45/29; 631/61/475/2290; 692/699/67/1536/1665; 82/51; 82/58; 82/80; 82/83; Animals; Antibodies; Autophagy; Autophagy-Related Protein 5 - metabolism; Biochemistry; Biomedical and Life Sciences; Carcinogenesis - metabolism; Carcinogenesis - pathology; Carcinoma, Squamous Cell - genetics; Carcinoma, Squamous Cell - pathology; Carcinoma, Squamous Cell - ultrastructure; Cell Biology; Cell Culture; Cell Line, Tumor; Cell migration; Cell Movement - genetics; Cell Proliferation - genetics; Disease Progression; Down-Regulation - genetics; Gene Expression Regulation, Neoplastic; Humans; Immunology; Life Sciences; Membrane Proteins - metabolism; Metastases; Mice, Inbred BALB C; Mice, Nude; Mouth Neoplasms - genetics; Mouth Neoplasms - pathology; Mouth Neoplasms - ultrastructure; Neoplasm Invasiveness; Oral cancer; Oral squamous cell carcinoma; Pathogenesis; Phagocytosis; Phenotypes; Protein Binding; Proteomics; Retinol-binding protein; Retinol-binding protein 1; Retinol-Binding Proteins, Cellular - metabolism; Signal Transduction; Squamous cell carcinoma; Therapeutic applications; Vacuoles - metabolism; Vacuoles - ultrastructure; Vitamin A; Xenografts
• ISSN: 2041-4889; 2041-4889
• DOI: 10.1038/s41419-020-2693-8

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.