Journal Article

ENO1 Promotes OSCC Migration and Invasion by Orchestrating IL-6 Secretion from Macrophages via a Positive Feedback Loop

Liu, Luyao, Lin, Ying, Li, Bo, Li, Weibo, Li, Yafei, Zhang, Wenwen

2023

Overview

Oral squamous cell carcinoma (OSCC) has a five-year survival rate of less than 50% due to its susceptibility to invasion and metastasis. Crosstalk between tumor cells and macrophages has been proven to play a critical role in tumor cell migration and invasion. However, the specific mechanisms by which tumor cells interact with macrophages have not been fully elucidated. This study sought to investigate the regulatory mechanism of tumor cell-derived alpha-enolase (ENO1) in the interaction between tumor cells and macrophages during OSCC progression. Small interfering RNA (siRNA) transfection and recombinant human ENO1 (rhENO1) stimulation were used to interfere with the interaction between tumor cells and macrophages. Our results showed that ENO1 was expressed higher in CAL27 cells than in HaCaT cells and regulated lactic acid release in CAL27 cells. Conditioned medium of macrophages (Macro-CM) significantly up-regulated the ENO1 mRNA expression and protein secretion in CAL27 cells. ENO1 promoted the migration and invasion of tumor cells by facilitating the epithelial–mesenchymal transition (EMT) through macrophages. ENO1 orchestrated the IL-6 secretion of macrophages via tumor cell-derived lactic acid and the paracrine ENO1/Toll-like receptor (TLR4) signaling pathway. In turn, IL-6 promoted the migration and invasion of tumor cells. Collectively, ENO1 promotes tumor cell migration and invasion by orchestrating IL-6 secretion of macrophages via a dual mechanism, thus forming a positive feedback loop to promote OSCC progression. ENO1 might be a promising therapeutic target which is expected to control OSCC progression.

• Publisher: MDPI
• Subject: Carcinoma, Squamous Cell - pathology / Cell Line, Tumor / Cell Movement - physiology / Cell Proliferation / DNA-Binding Proteins - genetics / DNA-Binding Proteins - metabolism / Epithelial-Mesenchymal Transition - genetics / Feedback / Head and Neck Neoplasms - metabolism / Humans / Interleukin-6 - genetics / Interleukin-6 - metabolism / Macrophages - metabolism / Mouth Neoplasms - pathology / Phosphopyruvate Hydratase - genetics / Phosphopyruvate Hydratase - metabolism / RNA, Small Interfering - metabolism / Squamous Cell Carcinoma of Head and Neck - metabolism