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

Bioengineered. 2022 Jan;13(1):1952-1961. doi: 10.1080/21655979.2021.2024336.

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.

Keywords: Cervix cancer (CC); EIF3D; FAK; GRP78; cancer stem cells (CSCS).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Line, Tumor
  • Cell Proliferation / genetics
  • Cervix Uteri / metabolism
  • Cervix Uteri / pathology
  • Endoplasmic Reticulum Chaperone BiP / genetics
  • Endoplasmic Reticulum Chaperone BiP / metabolism*
  • Eukaryotic Initiation Factor-3 / genetics
  • Eukaryotic Initiation Factor-3 / metabolism*
  • Female
  • Focal Adhesion Kinase 1 / genetics
  • Focal Adhesion Kinase 1 / metabolism*
  • Humans
  • Middle Aged
  • Neoplasm Metastasis / genetics
  • Neoplastic Stem Cells / metabolism*
  • Uterine Cervical Neoplasms* / genetics
  • Uterine Cervical Neoplasms* / metabolism
  • Uterine Cervical Neoplasms* / pathology

Substances

  • EIF3D protein, human
  • Endoplasmic Reticulum Chaperone BiP
  • Eukaryotic Initiation Factor-3
  • HSPA5 protein, human
  • Focal Adhesion Kinase 1
  • PTK2 protein, human

Grants and funding

This work was supported by Zunyi Science and Technology Cooperative (Grant no. 2017-41).