TP53INP1 down-regulation activates a p73-dependent DUSP10/ERK signaling pathway to promote metastasis of hepatocellular carcinoma

Identifying critical factors involved in the metastatic progression of hepatocellular carcinoma (HCC) may offer important therapeutic opportunities. Here we report that the pro-apoptotic stress response factor TP53INP1 is often selectively down-regulated in advanced stage IV and metastatic human HCC tumors. Mechanistic investigations revealed that TP53INP1 down-regulation in early stage HCC cells promoted metastasis via DUSP10 phosphatase-mediated activation of the ERK pathway. The DUSP10 promoter included putative binding sites for p73 directly implicated in modulation by TP53INP1. Overall, our findings showed how TP53INP1 plays a critical in limiting progression of early stage HCC, with implications for developing new therapeutic strategies to attack metastatic HCC.

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