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Patients with renal cell carcinoma (RCC) often develop distant metastasis and the specific molecular mechanism remains poorly understood. In our study, we demonstrated that MUC15, a subtype of mucins family, could suppress the progression of RCC by inhibiting PI3K/AKT signaling. Firstly, we observed that MUC15 was notably decreased in RCC compared to normal tissue. Furthermore, we showed that MUC15 could negatively modulate the migration and invasion of RCC in vitro and in vivo. Mechanistically, we found that knocking-down of MUC15 could active the PI3K/AKT signaling by increasing the AKT phosphorylation and subsequently increase the mRNA and protein expression of MMP2 and MMP9. Interruption of the AKT pathway with the specific inhibitor LY294002 could reverse the expression of MMPs. Therefore, our study clarify the novel function of MUC15 in RCC, which may provide a new sight to diagnose and prevent RCC metastasis.

MUC15 inhibits cancer metastasis via PI3K/AKT signaling in renal cell carcinoma