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核糖体整合在人乳腺癌细胞中诱导类似上皮-间质转化的现象并导致细胞周期停滞。

Ribosome Incorporation Induces EMT-like Phenomenon with Cell Cycle Arrest in Human Breast Cancer Cell.

作者信息

Kudo Mikiko, Anam Mohammad Badrul, Istiaq Arif, Ahmad Shah Adil Ishtiyaq, Ito Naofumi, Ohta Kunimasa

机构信息

Department of Stem Cell Biology, Faculty of Arts and Science, Kyushu University, Fukuoka, Japan.

Department of Developmental Neurobiology, Graduate School of Life Sciences, Kumamoto University, Kumamoto, Japan.

出版信息

Cells Tissues Organs. 2022;211(2):212-221. doi: 10.1159/000513908. Epub 2021 Feb 26.

Abstract

Although ribosomes are generally known to be a translational machinery, some ribosomal proteins also have accessory functions involving early development and differentiation. Previously, we reported that ribosome incorporation into human dermal fibroblasts generated embryoid body-like cell clusters, altered cellular fate, and differentiated into cells of all 3 germ layers. However, the molecular phenomena induced by ribosome incorporation in the cell remained unknown. Here, we demonstrate that ribosome incorporation into human breast cancer cell MCF7 leads to ribosome-induced cell clusters (RICs) formation accompanying with epithelial-mesenchymal transition (EMT)-like gene expression. Following ribosome incorporation, MCF7 cells cease proliferation, which is caused by inhibition of cell cycle transition from G0 to G1 phase. Further, MCF7 RICs show induced expression of EMT markers, TGF-β1 and Snail along with autophagy markers and tumor suppressor gene p53. These findings indicate that the incorporation of ribosome into cancer cells induces an EMT-like phenomenon and changes the cancer cell characteristics.

摘要

尽管核糖体通常被认为是一种翻译机制,但一些核糖体蛋白也具有涉及早期发育和分化的辅助功能。此前,我们报道将核糖体掺入人皮肤成纤维细胞会产生类胚体样细胞簇,改变细胞命运,并分化为所有三个胚层的细胞。然而,核糖体掺入细胞所诱导的分子现象仍然未知。在这里,我们证明将核糖体掺入人乳腺癌细胞MCF7会导致核糖体诱导的细胞簇(RICs)形成,并伴随上皮-间质转化(EMT)样基因表达。核糖体掺入后,MCF7细胞停止增殖,这是由细胞周期从G0期到G1期的转变受到抑制所致。此外,MCF7 RICs显示出EMT标志物、TGF-β1和Snail以及自噬标志物和肿瘤抑制基因p53的诱导表达。这些发现表明核糖体掺入癌细胞会诱导类似EMT的现象并改变癌细胞特征。

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