ROLE OF TYROSYLPROTEIN SULFOTRANSFERASE 2 (TPST2) IN PANCREATIC CANCER

Abstract

Pancreatic cancer is an aggressive disease which has become the third leading cause for cancer deaths in the United States. Tyrosylprotein sulfotransferase 2 (TPST2) is a post‐translational modification enzyme which locates in the trans‐Golgi apparatus and catalyzes the sulfation of proteins’ tyrosine residues. Moreover, tyrosine sulfation has been shown to play a critical role in protein‐protein interaction. By analyzing TCGA data, we found that the expression of several known substrates of TPST2 were affected in pancreatic cancer. However, whether TPST2 affects cancer cell behavior is unclear. To determine the role of TPST2 in pancreatic cancer, MTT cell growth assay and soft agar colony formation assay were performed to assess cancer cell proliferation in MiaPACA2 and PANC‐1 human pancreatic cancer cell lines. Migration and invasion of cancer cells in vitro were evaluated by transwell assay. CRISPR‐Cas9 was utilized to establish TPST2 KO stable cell lines. Total RNA‐seq analysis was performed to analyze the transcriptome in the TPST2 KO and control cells. We showed that knockdown of TPST2 inhibited the proliferation of pancreatic cancer cells both in vitro and in vivo. Knockdown of TPST2 also decreased migration and invasion of pancreatic cancer cells in vitro. RNA‐seq analysis revealed that the extracellular matrix (ECM) receptor interaction pathway was significantly downregulated in TPST2 KO cells. We further demonstrated that expression of intergrin beta 4 (ITGB4), a protein involved in ECM receptor interaction pathway, was decreased when TPST2 was knocked‐down or inhibited. Our studies have uncovered the role of protein sulfation in pancreatic cancer and may establish TPST2 as a therapeutic target for pancreatic cancer.Support or Funding InformationThis work was supported in part by National Institutes of Health grants DK083952, ES023438 to Wen Xie.