FBXO32 activates the PI3K/AKT pathway by inhibiting PTEN through ubiquitination of TAL1 in hepatocellular carcinoma.

The role of E3 ubiquitin ligases in cellular mechanisms and cancer progression is critical. In this study, our primary objective was to elucidate the functional consequences of F-box only protein 32 (FBXO32) in the progression and metastasis of hepatocellular carcinoma (HCC) and to clarify the signaling networks. FBXO32 was highly expressed, and T-cell acute lymphocytic leukemia protein 1 (TAL1) was poorly expressed in HCC cells relative to THLE-2 cells. FBXO32 interacted with the TAL1 protein and degraded TAL1. Knocking down FBXO32 suppressed epithelial-mesenchymal transition and the PTEN/PI3K/AKT signaling in MHCC-97H cells, while knocking down TAL1 reversed this effect. Similarly, overexpression of FBXO32 in SNU-398 cells promoted HCC progression, and reactivation of TAL1 also reversed this trend. Importantly, HCC patients with high FBXO32 or low TAL1 expression were both associated with poor prognosis. Our study has shown that FBXO32 facilitates HCC growth and metastasis via the PTEN/PI3K/AKT signaling through ubiquitination of TAL1. Consequently, FBXO32 emerges as a promising target for therapeutic intervention in the treatment of HCC.