SPP1 promotes the metastasis of liver cancer cells through modulation of the MT1L/vimentin axis.

Tumor metastasis, a hallmark of cancer progression including hepatocellular carcinoma (HCC), is closely linked to poor prognosis. Therefore, strategies to suppress tumor metastasis remain an unresolved challenge for improving patient care. We identified that the oncogenic gene secreted phosphoprotein 1 (SPP1) is highly expressed in HCC tissues. A pseudogene-derived long non-coding RNA, metallothionein 1L (MT1L), was found to be negatively regulated by SPP1. Clinically, MT1L expression was reduced in HCC specimens, and its higher expression correlated positively with favorable prognosis. Notably, MT1L expression was inversely correlated with SPP1 expression in HCC. Mechanistically, SPP1 suppressed MT1L expression through the integrin signaling pathway. Overexpression of MT1L inhibited cell motility and lipid accumulation by repressing vimentin expression. Furthermore, rescue experiments demonstrated that MT1L was functionally involved in SPP1-mediated effects. Collectively, our findings reveal a novel association among the SPP1/MT1L/integrin/vimentin axis in HCC progression, suggesting that targeting this pathway may represent a potential therapeutic approach for HCC.