Nucleostemin interacts with SMAD3 promoting tumor metastasis.

SMAD3 plays a crucial role in TGF-β, regulating various normal developmental mechanisms and disease pathogenesis. Here, we report that SMAD3 directly interacts with Nucleostemin (NS), leading to nuclear translocation and affecting SMAD3 activity after TGF-β1 stimulation. Moreover, NS acts as a competitor, preventing PPM1A from recognizing and dephosphorylating SMAD3. Experimental investigations have demonstrated that NS significantly enhances cellular migration and invasion by promoting the EMT mechanism in vitro. NS knockdown notably suppresses tumor metastasis in the lungs and liver in vivo. Importantly, NS expression is significantly elevated in numerous human malignancies, correlating with a poorer prognosis. The collective evidence from these studies suggests that NS exhibits oncogenic characteristics, supporting further exploration of NS as a potential target for tumor treatment.