FGFBP1, a downstream target of the FBW7/c-Myc axis, promotes cell proliferation and migration in pancreatic cancer.

Abstract

The secreted fibroblast growth factor (FGF) binding protein (FGF-BP), which is an extracellular chaperone molecule for FGFs, has been demonstrated to enhance the biological and biochemical activities of FGFs and to be closely related to the growth of several cancers. However, the role of FGFBP1 in pancreatic adenocarcinoma (PDAC) has not been studied extensively. We previously reported that decreased FBW7 could induce pancreatic cancer proliferation and progression. In the present study, we investigated whether FBW7 inhibited cell proliferation and metastasis by decreasing the expression of FGFBP1 in pancreatic cancer. We initially confirmed that pancreatic cancer patients with higher FGFBP1 expression had a worse prognosis. Next, we demonstrated that FGFBP1 silencing inhibited the proliferation and metastasis of PANC-1 and Mia PaCa-2 cells. Mechanistically, FGFBP1 was negatively correlated with FBW7 but positively correlated with c-Myc in PDAC tissue samples, and FBW7 regulated FGFBP1 in a c-Myc-dependent manner. We also found that FBW7 silencing could partly reverse the effect of FGFBP1 silencing on proliferation and metastasis. In summary, FGFBP1 is a prognostic marker for overall survival and is required for pancreatic cancer cell proliferation and metastasis, which is mediated by FBW7 in a c-Myc-dependent manner. Thus, targeting the FBW7/c-Myc/FGFBP1 axis might suppress recurrence and metastasis and provide novel treatment strategies for PDAC.