FOXO3 and pancreatic neoplasm: SIRT1 or CUL4B knockdown in PANC-1 cells decreased cell invasion potential, which was partially rescued via the co-knockdown of FOXO3 or GRHL3, indicating that the SIRT1/CRL4B complex could promote pancreatic cancer invasion through repression of FOXO3 and GRHL3 (Fig. 5J).