研究动态
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金属蛋白酶ADAMTS12对宫颈癌细胞表型的影响及其潜在机制。

Effects of metalloprotease ADAMTS12 on cervical cancer cell phenotype and its potential mechanism.

发表日期:2023 Aug 29
作者: Ruanmin Zou, Ruihong Gu, Xinyu Tu, Jiani Chen, Songjun Liu, Xiangyang Xue, Wensu Li, Yuyang Zhang
来源: TROPICAL MEDICINE & INTERNATIONAL HEALTH

摘要:

ADAMTS12是一种广泛表达于人类组织中的基因。我们研究了ADAMTS12在宫颈癌组织中的表达水平及其与临床病理特征的关系。我们还探究了ADAMTS12在宫颈癌细胞中的功能及其潜在机制。我们发现癌组织中ADAMTS12的表达水平较高,与更糟糕的总生存率相关。免疫荧光实验显示宫颈癌细胞的细胞质是ADAMTS12主要的表达位点。在HeLa和CaSki细胞中过表达ADAMTS12显著促进了细胞增殖、迁移和侵袭。我们发现2032个基因与ADAMTS12相关,主要涉及细胞外基质、TGF-β信号通路。ADAMTS12过表达细胞中mTOR和4E-BP1的磷酸化水平上调。免疫共沉淀结合蛋白质质谱分析从ADAMTS12过表达的HeLa细胞中筛选出ADAMTS12与TGF-β信号通路相关蛋白的相互作用。因此,我们得出结论,ADAMTS12可能通过与TGF-β1相互作用,影响mTOR信号通路,并进而影响宫颈癌细胞的生物功能。©2023.Springer Science+Business Media,LLC.
ADAMTS12 is a gene widely expressed in human tissues. We studied the expression level of ADAMTS12 in cervical cancer tissue and its relationship with clinicopathological features. We also explored the function of ADAMTS12 in cervical cancer cells and its underlying mechanisms. We found the higher expression level of ADAMTS12 in cancer tissues, which was associated with the worse overall survival rate. The immunofluorescence assay showed that the cytoplasm of cervical cancer cells is the main expression site of ADAMTS12. Overexpression of ADAMTS12 in HeLa and CaSki cells prominently promoted the cell proliferation, migration and invasion. We found that 2032 genes were correlated with ADAMTS12, which was mainly related to extracellular matrix, TGF-β signaling pathway. The phosphorylation levels of mTOR and 4E-BP1 were upregulated in ADAMTS12-overexpressing cells. Co-Immunoprecipitation combined with protein mass spectrometry showed that TGF-β signaling pathway-related proteins interacting with ADAMTS12 were screened from HeLa cells with ADAMTS12 overexpression. Therefore, we concluded that ADAMTS12 may affect the mTOR signaling pathway through the interacting with TGF-β1, and then affect the biological function of cervical cancer cells.© 2023. Springer Science+Business Media, LLC.