Zeb1 for RCP-induced oral cancer cell invasion and its suppression by resveratrol

Abstract

Rab coupling protein (RCP) is upregulated in head and neck squamous cell carcinoma (HNSCC) and is correlated with the progression and survival of patients. However, the role of RCP in one of the aggressive types of HNSCC, oral squamous cell carcinoma (OSCC), remains elusive. In the present study, we identified the important role of Zeb1 in RCP-induced OSCC epithelial-to-mesenchymal transition (EMT) and invasion. RCP induces Zeb1 expression, and silencing Zeb1 expression significantly inhibits RCP-induced OSCC invasion. In addition, Zeb1 upregulates MT1-MMP expression to promote OSCC EMT and invasion. Furthermore, we observed that the β1 integrin/EGFR/β-catenin signaling cascade mediates RCP-induced Zeb1 expression to promote OSCC invasion. Notably, we provide evidence that resveratrol (REV) strongly inhibits RCP-induced Zeb1 expression through blocking β1 integrin endosome recycling and EGFR activation, leading to suppression of RCP-induced OSCC invasion, demonstrating the important role of RCP in OSCC invasion and its reversion by REV. Collectively, the present study provides evidence for the first time that RCP aggravates OSCC invasion through increasing Zeb1 expression and subsequently upregulating MT1-MMP expression and that this process is reversed by REV, providing novel biomarkers and indicating the therapeutic potential of REV in OSCC.

CircRTN4 promotes pancreatic cancer progression through a novel CircRNA-miRNA-lncRNA pathway and stabilizing epithelial-mesenchymal transition protein

“…RAB11FIP1 plays important roles in promoting cancer migration and invasion through regulating the expression of EMT-related proteins (Supplementary Fig. 8 A -C) [ 31 , 32 ]. Therefore, we hypothesized that circRTN4 stabilizes RAB11FIP1 in regulating EMT in PDAC.…”

“…Several studies reported that the upregulation of RAB11FIP1 and RAB11FIP2 and their interacting partner RAB11a promotes cancer migration and invasion [ 26 – 29 ]. RAB11FIP1 protects integrins from degradation, regulates cadherin recycling and promotes the expression of EMT-related transcription factors [ 27 , 29 , 31 , 32 , 61 , 62 ]. In this study, we found that circRTN4 promotes EMT via RAB11FIP1-mediated upregulation of N-cadherin, Slug, Snai1, Twist and Zeb1 in PDAC.…”

Rab11-FIP1/RCP Functions as a Major Signalling Hub in the Oncogenic Roles of Mutant p53 in Cancer

“…We and others have shown that the cooperation of integrin b1 and EGFR is dependent on Rab11-FIP1 (13,16,20,21). In some cells, this was dependent on stimulation with the EGFR ligand EGF, or with the avb3 integrin ligand osteopontin (13).…”

Plant-Based Antioxidant Extracts and Compounds in the Management of Oral Cancer

“…A recent study reported that Rab coupling protein (RCP) induces OSCC invasion and EMT by expressing Zeb1 and MT1-MMP. Resveratrol was reported to inhibit RCP-induced OSCC invasion by downregulating Zeb1 and β1 integrin expression [ 78 ].…”