Overexpression of Eukaryotic translation initiation factor 3D induces stem cell-like properties and metastasis in cervix cancer by activating FAK through inhibiting degradation of GRP78

Abstract

Cervix cancer (CC) is the most common gynecological malignancy and the leading cause of morbidity among women worldwide. Previous study indicated that cancer stem cells (CSCs) existed in cervix cancer, and suppressing CSC characteristics of cervix cancer is needed to combat this disease. Eukaryotic translation initiation factor 3 (EIF3) is one of the most complex eukaryotic translation initiation factors containing 13 subunits (EIF3A-EIF3M) and it regulates eukaryotic translation. One member of EIF3, EIF3D, plays a role in the progression and development of multiple tumors. However, its possible role in cervix cancer progression is still unclear. In this study, we found the high EIF3D expression in human cervix cancer tissues. We further found that downregulation of EIF3D suppressed the proliferation and motility of cervix cancer cells. Furthermore, its downregulation restrained the stem cell-like properties of cervix cancer cells. Mechanically, we found that EIF3D promoted FAK activation through GRP78 in cervix cancer cells, thus contributing to the progression of cervix cancer. Therefore our results suggested that EIF3D could serve as a promising target of cervix cancer.