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.

Identification and Validation of m7G-Related Prognostic Signatures and Associated Regulatory Axis in Head and Neck Squamous Cell Carcinoma

“…Knocking down EIF3D can inhibit the proliferation and invasion of breast cancer cells by inhibiting the activation of the Wnt/β-catenin signal pathway [69]. Overexpression of EIF3D induces stem cell-like characteristics and metastasis in cervical cancer cells by inhibiting GRP78 degradation and activating FAK [70]. EIF1 is a 12kDa protein that plays many important roles in translation initiation in eukaryotes.…”

A novel prognostic 7-methylguanosine signature reflects immune microenvironment and alternative splicing in glioma based on multi-omics analysis

“…EIF3D is a subunit of EIF3 that facilitates the cap-dependent translation of approximately 20% of mRNA ( de la Parra et al, 2018 ). EIF3D was widely studied in cancer and was known to promote the progression of cervical cancer ( Zhong and Lan, 2022 , 78), gallbladder cancer ( Zhang et al, 2017 ), and renal cell carcinoma ( Pan et al, 2016 ; Huang et al, 2019 ). Besides, EIF3D might serve as an independent poor prognostic marker in lung adenocarcinoma ( Wang et al, 2019 )…”

eIF3d: A driver of noncanonical cap–dependent translation of specific mRNAs and a trigger of biological/pathological processes

“…Morphological abnormalities and unlimited proliferation are common hallmarks of tumor cells ( 52 , 53 ). Examination of human cancer tissues has revealed that eIF3d expression is upregulated in many cancers including cancers of breast ( 54 ), prostate ( 55 ), ovary ( 56 ), gallbladder ( 21 ), stomach ( 57 ), bladder ( 58 ), colon ( 59 ), lung ( 60 ), and cervix ( 61 ) as well as in glioma ( 62 ), renal cell carcinoma ( 63 ), and chronic hepatitis C–associated hepatocellular carcinoma ( 64 ). These findings suggest that eIF3d may associate with tumorigenesis or cancer cell proliferation.…”

“…5 C ). First, ectopic overexpression of eIF3d significantly promoted the proliferation, migration, and stem cell–like properties of cervical cancer cells via activating the glucose-regulated protein 78 (GRP78)–focal adhesion kinase pathway ( 61 ). Similar findings have been made with ectopic eIF3d overexpression in colon cancer cells in which increased cell proliferation was observed as determined using colony formation, MTT, and soft-agar assays ( 59 ).…”