PKP3 interactions with MAPK-JNK-ERK1/2-mTOR pathway regulates autophagy and invasion in ovarian cancer

Abstract Armadillo-related proteins function in both signal transduction and cell adhesion, it also plays a central role in tumorigenesis. Plakophilin 3 (PKP3) is a member of the armadillo protein family. PKP3 has demonstrated a role in melanoma, breast cancer, gastric cancer, and other kind of cancers; however its role in ovarian cancer was not fully understood. In this study we explored the function and mechanisms of PKP3 in ovarian cancer. An elevated level of PKP3 was found in ovarian cancer tissues compared with normal tissues. PKP3 also modulate cellular proliferation and invasion in ovarian cancer. The ability of cellular proliferation, formation, and invasion was significantly decreased after the silencing of PKP3 in SKOV3 cells. While an over-expression of PKP3 in A2780 cells up-regulates the ability of cellular proliferation, formation, and invasion. As for the mechanism of PKP3, mTOR pathway was activated to regulate autophagy according to the interaction of PKP3 with the upstream of MAPK pathway. The result of this study support PKP3 as the oncogene candidate and a potential target for the treatment of ovarian cancer.