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真核翻译起始因子 3D 的过表达通过抑制 GRP78 的降解激活 FAK,从而诱导宫颈癌中具有干细胞样特性和转移。

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.

机构信息

Department of Gynecologic Oncology, Linyi Cancer Hospital, Linyi, Shandong Province, China.

Department of Gynecology, The First People's Hospital of Zunyi (The Third Affiliated Hospital of Zunyi Medical University), Zunyi, Guizhou Province, China.

出版信息

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.

摘要

宫颈癌(CC)是最常见的妇科恶性肿瘤,也是全球女性发病率最高的疾病。先前的研究表明,宫颈癌中存在癌症干细胞(CSC),抑制宫颈癌的 CSC 特征是对抗这种疾病的必要手段。真核翻译起始因子 3(EIF3)是最复杂的真核翻译起始因子之一,包含 13 个亚基(EIF3A-EIF3M),它调节真核翻译。EIF3 的一个成员 EIF3D 在多种肿瘤的进展和发展中发挥作用。然而,其在宫颈癌进展中的可能作用尚不清楚。在这项研究中,我们发现人宫颈癌组织中 EIF3D 的高表达。我们进一步发现,下调 EIF3D 抑制了宫颈癌细胞的增殖和迁移。此外,它的下调抑制了宫颈癌细胞的干细胞样特性。在机制上,我们发现 EIF3D 通过 GRP78 在宫颈癌细胞中促进 FAK 的激活,从而促进宫颈癌的进展。因此,我们的结果表明 EIF3D 可以作为宫颈癌有前途的治疗靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ee1a/8806159/b97d20fb5011/KBIE_A_2024336_UF0001_OC.jpg

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