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SMAP1 promotes hepatoblastoma cell proliferation by modulating the C-Kit-activated ERK/MAPK pathway
Jie Liu1,2, Ke Xu3, Hongyue Wang3
1Department of Pediatric Surgery, The First Affiliated Hospital of Wannan Medical University (Yijishan Hospital of Wannan Medical University), Wannan Medical University, Wuhu, China.
None:
Hepatoblastoma (HB) is the most common pediatric liver malignancy. We investigated the role of SMAP1 in HB proliferation and its mechanism. Sixty-seven HB tissues were analyzed for SMAP1 expression via immunohistochemistry and correlated with clinical outcomes. qRT-PCR quantified SMAP1 mRNA in HB cell lines versus normal hepatocytes. SMAP1 was knocked down (siRNA/lentivirus) or overexpressed (plasmid) in HB cells; proliferation was assessed by CCK-8 and colony formation. A nude-mouse xenograft model was used to evaluate tumorigenicity. Western blotting determined C-Kit and ERK/MAPK pathway activity after SMAP1 modulation. Rescue experiments used ERK activator C16-PAF, inhibitor U0126, or C-Kit inhibitor ISCK03. SMAP1 was upregulated in HB and predicted poor prognosis. Knockdown reduced C-Kit, p-C-Kit, and p-ERK1/2, inhibited proliferation and colony formation, and suppressed xenograft growth. Overexpression produced opposite effects. U0126 reversed ERK1/2 phosphorylation and p-Rb in SMAP1-overexpressing cells, whereas C16-PAF restored ERK signaling and c-Myc/p-Rb in knockdown cells. ISCK03 blocked C-Kit/ERK activation prompted by SMAP1 overexpression. SMAP1 drives HB progression by activating C-Kit-ERK/MAPK signaling, representing a potential therapeutic target.
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