p8 Expression controls pancreatic cancer cell migration, invasion, adhesion, and tumorigenesis

Abstract

p8 is a stress gene whose activity is necessary for tumor development and progression. The acquisition of invasive properties by transformed cells is a key event in tumor development. In order to establish whether p8 is involved or not in this phenomenon, we assessed the capacity of p8 at influencing cell adhesion, migration, invasion, and tumorigenesis of pancreatic cancer cells. p8 expression was knocked down by a small interfering RNA (siRNA) in pancreatic cancer-derived Panc-1 and MiaPaCa-2 cells and subsequent changes in cell adhesion, migration, invasion, and tumorigenesis were assessed. Influence of p8 silencing on gene expression was analyzed using cDNA microarrays. The influence of inhibiting CDC42, one of the genes most over-expressed in p8-silenced cells, on the changes observed in p8-silenced cells was also evaluated. Finally, the tumorigenic capacities of Panc-1 cells transfected with control siRNA or p8 siRNA were compared by assessing their ability to form colonies in soft agar and to grow as xenografts in nude mice. Knocking-down p8 in pancreatic cancer cells in vitro decreased migration and invasion while increasing cell adhesion; over-expression produced the opposite effect. Knocking down CDC42 reversed almost completely the effects of silencing p8 in vitro. Finally, cells transfected with p8 siRNA were almost unable to form colonies in soft agar. In addition, p8-deficient Panc-1 cells did not develop tumors when injected subcutaneously in nude mice. In conclusion, p8 expression controls pancreatic cancer cell migration, invasion and adhesion, three processes required for metastasis, at least in part, through CDC42, a major regulator of cytoskeleton organization.

Nupr1-Aurora Kinase A Pathway Provides Protection against Metabolic Stress-Mediated Autophagic-Associated Cell Death

“…1C). Several functions, including cell transformation (6), inhibition of apoptosis (11), regulation of migration (9), and promotion of resistance to antitumoral treatments (10) have been attributed to Nupr1, all of them pointing at a protumoral activity. In this study, we report a novel role for Nupr1 in the cell response to metabolic stress, which is to favor cell survival by inhibiting autophagic cell death through AURKA expression.…”

“…Protein extraction was conducted on ice using total protein extraction buffer as previously reported (9). Protein samples (80 mg) were denaturated at 95 C and subsequently separated by 12.5% SDS-PAGE.…”

“…Nupr1 is a stress response protein systematically overexpressed in pancreatic cancer and associated with bad prognosis (6,7). Nupr1 regulates TGF-b responsiveness, inhibits apoptosis, and promotes cancer cell resistance to antitumoral treatments (8)(9)(10)(11)(12). We hypothesized that, under chronic hypoxic conditions as well as nutrient starvation, pancreatic cancer cells activate intracellular pathways responsible for their resistance.…”

Nidogen 1 and Nuclear Protein 1: novel targets of ETV5 transcription factor involved in endometrial cancer invasion

“…Primary antibodies used in this study were anti-ETV5 (sc-22807, Santa Cruz Biotechnologies, Santa Cruz, CA, USA), anti-NID1 (anti-hNidogen1, MAB2570, R&D Systems, Minneapolis, MN USA), anti-Nupr1 [15] and anti atubulin (2125, Cell Signalling, Danvers, MA). NID1 immunoblot was performed on secreted proteins isolated from media.…”

Effect of Tea Polyphenols on the Adhesion of Highly Metastatic Human Lung Carcinoma Cell Lines to Endothelial Cells in Vitro

“…The invasion and metastasis of tumor cells are a complex pathological process, in which the cell adhesion is involved in the entire procedure Sandi et al, 2011). The mediating adhesion of cells to other cells is a broad family of cell adhesion molecules, which not only mediate the adhesion of tumor cells to extracellular matrix, but also participate in the interactions between tumor cells and vascular endothelial cells, leucocyte, platelets, solid organ cells or other cells (Albelda 1993;Hamburger et al, 1990;Polley et al, 1991;Gassmann and Haier 2008;Beiras-Fernandez 2009).…”