Prostasin may contribute to chemoresistance, repress cancer cells in ovarian cancer, and is involved in the signaling pathways of CASP/PAK2-p34/actin.

Abstract

Ovarian cancer is the deadliest of gynecologic cancers, largely due to the development of drug resistance in chemotherapy. Prostasin may have an essential role in the oncogenesis. In this study, we show that prostasin is decreased in an ovarian cancer drug-resistant cell line and in ovarian cancer patients with high levels of excision repair cross-complementing 1, a marker for chemoresistance. Our cell cultural model investigation demonstrates prostasin has important roles in the development of drug resistance and cancer cell survival. Forced overexpression of prostasin in ovarian cancer cells greatly induces cell death (resulting in 99% cell death in a drug-resistant cell line and 100% cell death in other tested cell lines). In addition, the surviving cells grow at a much lower rate compared with non-overexpressed cells. In vivo studies indicate that forced overexpression of prostasin in drug-resistant cells greatly inhibits the growth of tumors and may partially reverse drug resistance. Our investigation of the molecular mechanisms suggests that prostasin may repress cancer cells and/or contribute to chemoresistance by modulating the CASP/P21-activated protein kinase (PAK2)-p34 pathway, and thereafter PAK2-p34/JNK/c-jun and PAK2-p34/mlck/actin signaling pathways. Thus, we introduce prostain as a potential target for treating/repressing some ovarian tumors and have begun to identify their relevant molecular targets in specific signaling pathways.

• Authors: B-x Yan, J-x Ma, J Zhang, Y Guo, M D Mueller, S C Remick, J J Yu
• Journal: Cell death & disease (Cell Death Dis) Vol. 5 Pg. e995 (Jan 16 2014) ISSN: 2041-4889 [Electronic] England
• PMID: 24434518 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Actins
• Antineoplastic Agents
• PAK2 protein, human
• p21-Activated Kinases
• Serine Endopeptidases
• prostasin
• Caspases
• Cisplatin

Topics

• Actins (metabolism)
• Antineoplastic Agents (pharmacology)
• Caspases (genetics, metabolism)
• Cisplatin (pharmacology)
• Drug Resistance, Neoplasm
• Female
• Gene Expression Regulation, Neoplastic
• Humans
• Ovarian Neoplasms (drug therapy, enzymology, genetics, metabolism)
• Serine Endopeptidases (genetics, metabolism)
• Signal Transduction
• Tumor Cells, Cultured
• p21-Activated Kinases (genetics, metabolism)