Nuclear localization of tricellulin promotes the oncogenic property of pancreatic cancer

Abstract

Accumulating evidence has shown that dysregulation of tight junctions (TJs) is involved in tumor development and progression. In this study, we investigated the expression and subcellular distribution of tricellulin, which constitutes tricellular TJs, using human pancreatic adenocarcinomas. In well-differentiated pancreatic adenocarcinoma tissues, tricellulin immunostaining was prominent in the cytoplasm and the plasma membrane. In contrast, in poorly differentiated tissues, its immunostaining was predominantly observed in the nuclei and was almost absent in the plasma membrane. The distinct immunostaining of tricellulin successfully distinguished poorly differentiated adenocarcinoma from moderately and well-differentiated adenocarcinomas with high levels of sensitivity and specificity. Nuclear tricellulin expression significantly correlated with lymph node metastasis, lymphatic invasion and poor survival. In pancreatic cancer cell lines, tricellulin localization shifted from the membrane to nucleus with decreasing differentiation status. Nuclear localization of tricellulin promoted cell proliferation and invasiveness possibly in association with MAPK and PKC pathways in pancreatic cancers. Our results provide new insights into the function of tricellulin, and its nuclear localization may become a new prognostic factor for pancreatic cancers.

Estrogen/GPR30 Signaling Contributes to the Malignant Potentials of ER-Negative Cervical Adenocarcinoma via Regulation of Claudin-1 Expression

“…After incubation with a blocking buffer [0.01 mol/l PBS containing 5% bovine serum albumin (Sigma)], the sections were incubated with a rabbit polyclonal anti-Ki-67 (1:100, BioGenex) or anti-cleaved caspase-3 antibody (1:100, Cell Signaling Technology) at 4°C. Immunocytochemical labeling was visualized using the EnVision system according to the manufacturer's protocol [19] . The sections were counterstained with Meyer's hematoxylin.…”

“…BrdU incorporation assay was performed as described previously [19] . In the WST-8 assay, cells were seeded in 96-well plates, and their viability was assessed at 24 hours after incubation by using a Cell Counting Kit-8 (Dojindo Laboratories, Kumamoto, Japan) according to the manufacturer's instructions.…”

Prognostic significance of the co-expression of EGFR and HER2 in adenocarcinoma of the uterine cervix

“…Primary antibodies were EGFR (31G7, Nichirei, x100), HER2/ner (4B5, Roche, x100) and c-Met (D1C2, Cell Signaling, x100). Secondary antibody and detection was Dako Real TM EnVision TM detection system (EGFR and c-Met) and Ventana iVIEW DAB detection kit (HER2) [ 37 ].…”

Association of tricellulin expression with poor colorectal cancer prognosis and metastasis

“…Tricellulin localizes at tricellular tight junctions as a member of the tight-junction-associated MARVEL protein (TAMP) family (33). Nuclear or cytoplasmic tricellulin expression was associated with pancreatic cancer cell invasion and metastasis as well as a poor prognosis (17).…”

“…that nuclear tricellulin expression was associated with poorly differentiated pancreatic cancer and invasion of pancreatic cancer cells (17). To date, few studies have investigated the role of tricellulin in human cancers.…”