SATB1 Promotes Pancreatic Cancer Growth and Invasion Depending on MYC Activation

Abstract

BACKGROUND: SATB1 plays an important role in human malignant progression, inducing cancer cell proliferation and metastasis by regulating downstream gene expressions. However, little is known about the underlying mechanisms in which SATB1 promotes pancreatic cancer tumorigenesis. AIMS: To investigate SATB1 expression levels and its biological functions in promoting pancreatic cancer growth and invasion. METHODS: SATB1 expression levels were detected in seven human pancreatic cancer cell lines and 16 pairs of normal pancreatic/pancreatic cancer tissues using RT-PCR and western blot. SW1990 or Capan-1 cells stably knockdown (shRNA) or transiently knockdown (siRNA) SATB1 cells, and PANC-1 stably overexpressing SATB1 cells were investigated with MTT, EdU assay, flow cytometry, and transwell invasion assay for cell proliferation and invasion activity. The binding of SATB1 to MYC promoter region was examined using reporter assay. Expression of SATB1 in 68 pancreatic cancer samples was studied by immunohistochemical staining and scoring. RESULTS: SATB1 was overexpressed in pancreatic cancer tissues samples, showing strong correlation with pancreatic cancer invasion depth and tumor staging. SATB1 induced MYC mRNA and protein expression; promoted pancreatic cancer cell growth; increased cell population in S phase; and enhanced pancreatic cancer cell invasion in vitro. On the other hand, SATB1 knockdown showed opposite effects. Furthermore, MYC blocking in SATB1-overexpressing cells attenuated the promotion of pancreatic cancer cell growth and invasion. Our data also indicated that SATB1 bound to specific promoter region of MYC. CONCLUSIONS: SATB1 is overexpressed in pancreatic cancer, promoting cancer cell proliferation and invasion through the activation of MYC.