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

Abstract

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.

The molecular feature of macrophages in tumor immune microenvironment of glioma patients

“…M2 macrophage-secreted CHI3L1 could promote gastric and breast cancer metastasis [42] , and CHI3L1 modulates an immune suppressive microenvironment by reprogramming M2-like TAM in GBM [43] . TNFAIP6, RBP1, FBXO17, and GPX8 promote metastasis and invasiveness of tumor [44] , [45] , [46] , [47] . SLC43A3 and ADAM12 have been revealed as the biomarker and therapeutic target in tumor patients [48] , [49] .…”

Autophagy Process in Trophoblast Cells Invasion and Differentiation: Similitude and Differences With Cancer Cells

“…As mentioned, the role of autophagy in tumor development is controversial and dependent of the tumor characteristics and stage of tumor development (266). Briefly, it has been suggested that autophagy could promote aggressive characteristics of cancer cells such as increased cellular invasion (11,12), but it also represents a barrier for cancer proliferation (13)(14)(15). In cancer cells, the inhibition of autophagy results in impaired metabolism proliferation, survival, and spontaneous tumor malignancy depending not only on the tumor type but also of its temporal development (267).…”

“…Indeed, the role of autophagy in tumor development is controversial and dependent on tumor stage and type. It has been suggested that autophagy could promote aggressive characteristics of cancer cells, such as increased cellular invasion (11,12), but also be a barrier to cancer proliferation (13)(14)(15). Additionally, autophagy also provides the microenvironment for placentation and cancer growth.…”

Model establishment of prognostic-related immune genes in laryngeal squamous cell carcinoma

“…It is reported that RBP1 affects retinoic acid metabolism and leads to cell differentiation and tumor progression by reducing retinol transport and preventing retinol ester formation and nuclear retinoic acid receptor (RARs) activity. [ 22 ] BTC is one of the least-known ligands among endogenous EGFR ligands. BTC promotes wound healing better by promoting cell migration, but it reduces receptor affinity and attenuates the induction of EGFR phosphorylation, which is thought to be related to cancer progression.…”