IGF2BP3 promotes esophageal squamous cell carcinoma progression by regulating global protein translation

Esophageal squamous cell carcinoma (ESCC) has a consistently high incidence and poor prognosis. The RNA-binding protein insulin-like growth factor 2-binding protein 3 (IGF2BP3) has been implicated in the progression of various malignant tumors. However, the contribution of IGF2BP3 in ESCC and its underlying molecular mechanisms remain elusive. Here, we found that IGF2BP3 was upregulated in ESCC tissues, and elevated IGF2BP3 expression correlates with reduced overall survival. Through gain- and loss-of-function assays, IGF2BP3 significantly enhanced ESCC cell proliferation and migration in vitro and accelerated tumor growth and metastasis in vivo. Mechanistically, IGF2BP3 directly binds to multiple ribosomal protein L (RPL) mRNAs (e.g., RPL12, RPL8, RPL17) and enhances their stability, thereby promoting ribosomal assembly and improving global translation efficiency. This leads to substantial upregulation of oncoproteins such as c-Myc and β-catenin. Collectively, our findings reveal an oncogenic role of IGF2BP3 in ESCC progression and highlight it as a promising molecular target for further therapeutic exploration in ESCC.