Constitutive Suppression of PRL-3 Inhibits Invasion and Proliferation of Gastric Cancer Cell in vitro and in vivo

Abstract

Objective: Overexpression of phosphatase of regenerating liver-3 (PRL-3) has been implicated in tumor progression and metastasis of gastric carcinoma. Here we examined what alterations occur in the phenotype of gastric cancer cells in vitro and in vivo when PRL-3 expression is knocked down. Methods: We constructed a small interfering RNA (siRNA)-expressing vector which stably interfered with PRL-3 expression and was transfected into SH101-P4 cells, which express the highest PRL-3 mRNA levels among 13 gastric cancer cell lines. The new SH101-P4 subclones, in which PRL-3 was stably reduced, were established and their in vitro growth, motility and abilities of liver metastasis from the injected spleen were analyzed in vivo. Results: PRL-3 knockdown effectively suppressed invasion and growth of SH101-P4 cells in vitro. Liver metastasis in vivo was significantly decreased when PRL-3 expression was suppressed. The primary tumor size in the injected spleen tended to be smaller in PRL-3 knockdown clones than in the controls. These findings suggest that PRL-3 expression may contribute not only to the establishment of metastasis but also to the growth of primary foci of human gastric cancer. Therefore, PRL-3 may be one of the target molecules in gastric cancer therapy.

PTP4A3 Independently Predicts Metastasis and Survival in Upper Tract Urothelial Carcinoma Treated with Radical Nephroureterectomy

“…Transient PTP4A3 knockdown by small interfering RNA has been shown to reduce cell proliferation, migration and invasion. 24 In a PTP4A3 gene deletion animal model PTP4A3 deficient mice had decreased angiogenesis, endothelial cell motility and vascular permeability. 20 The investigators also found that PTP4A3 null mice were viable and had no obvious gross abnormalities, implying that the side effects of PTP4A3 inhibition may be limited.…”

Phosphatase of regenerating liver: a novel target for cancer therapy

“…Up-regulated PRL-3 has been found in gastric carcinomas and was found to be significantly correlated to lymph node metastasis (25,26,27,28,29,30,31). Ovarian (32,33), liver (34,35), oral (36), cervical (37), esophageal (38), lung cancer (39,40), multiple myeloma (9,41), acute myeloid leukemia (AML) (42,43), and nasopharyngeal cancer (44) virtually all have been shown to exhibit high levels of PRL-3 expression.…”

PRL-3 promotes the proliferation of LoVo cells via the upregulation of KCNN4 channels

“…For example, overexpression of PRL-3 has been associated with metastasis of gastric cancer and human myeloma cells (5,6). In addition, small interfering RNA significantly inhibited the metastasis of B16-BL6 mouse melanoma cells and gastric cancer cells (7,8). Apart from that, PRL-3 has been proven to promote the growth of ovarian cancer (9).…”