上皮至间充质转化的状态与超微结构特征以及患者源头口腔癌细胞系中的TP53突变相关。
Epithelial-to-mesenchymal transition status correlated with ultrastructural features, and TP53 mutation in patient-derived oral cancer cell lines.
发表日期:2023 Aug 28
作者:
Sushant S Navarange, Sanjay M Bane, Darshan Mehta, Sanket Shah, Sanjay Gupta, Sanjeev K Waghmare
来源:
Cellular & Molecular Immunology
摘要:
口腔鳞状细胞癌(OSCC)在印度次大陆十分常见。OSCC患者的主要死因是转移。上皮间质转化(EMT)标志着转移过程中的一个重要步骤。另外,TP53作为一个重要的肿瘤抑制基因,也是治疗结果的重要决定因素,并且在EMT中也起到一定的作用。因此,了解超微结构特征、EMT状态和TP53突变状态之间的相互关系具有极其重要的意义。
我们通过透射电子显微镜观察了五种OSCC细胞系的超微结构。利用透过孔侵袭和迁移实验以及划痕实验,以及各种EMT相关基因的表达来评估细胞系的EMT状态。我们扩增了ACOSC3、ACOSC4和ACOSC16细胞系的TP53外显子,并进行了测序,通过序列比对鉴定出基因中的突变。UPCI:SCC029B细胞系的TP53突变已经有报道,而UPCI:SCC040则报道为野生型TP53。ACOSC4细胞系显示出最短的细胞间隙,同时具有最低的侵袭和迁移潜力。有趣的是,ACOSC4表现出最高的E-cadherin表达和最低的Vimentin、TWIST1、ZEB1和MMPs表达。此外,ACOSC4的TP53基因未突变,而ACOSC3和ACOSC16则携带了TP53突变。ACOSC3(R196*)的突变也在7个TCGA样本中发现。同样,UPCI:SCC040细胞系携带野生型TP53,显示较短的细胞内间隙。
细胞迁移特性与细胞超微结构、上皮间质转化状态以及基因组中TP53突变的状态相关。
©2023. 作者授权给施普林格自然有限公司独家使用。
Oral Squamous Cell Carcinoma (OSCC) is a highly prevalent cancer in the Indian subcontinent. The major cause of mortality in OSCC patients is metastasis. Epithelial-to-mesenchymal transition (EMT) marks an important step in the metastatic process. Additionally, TP53, an important tumor suppressor gene, is also a significant determinant of the treatment outcome, and also plays a role in EMT. Therefore, understanding the interconnections between ultrastructural features, EMT status and TP53 mutational status is of vital importance.The ultrastructure of five OSCC cell lines was visualized by transmission electron microscopy. Trans-well invasion and migration assays as well as scratch-wound assay, and the expression of various EMT-related genes were utilized to assess the EMT status of the cell lines. The TP53 exons were amplified for the ACOSC3, ACOSC4 and ACOSC16 cell lines and sequenced and the mutations in the gene were identified by sequence alignment. The TP53 mutation in the UPCI:SCC029B cell line has been previously reported, while UPCI:SCC040 has been reported to harbor a wild type TP53. The ACOSC4 cell line which showed the shortest intercellular gaps, also had the least invasive and migratory potential. Interestingly, ACOSC4 showed the highest expression of E-cadherin and the lowest expression of Vimentin, TWIST1, ZEB1, and MMPs. Additionally, TP53 gene of ACOSC4 was unmutated, whereas the ACOSC3 and ACOSC16 harbored TP53 mutations. The mutation in ACOSC3 (R196*) was also found in 7 TCGA samples. Similarly, the UPCI:SCC040 cell line that harbors a wild type TP53 showed shorter intracellular gaps.Cellular migratory properties are associated with cellular ultrastructure, epithelial-to-mesenchymal transition status and the status of TP53 mutation in the genome.© 2023. The Author(s), under exclusive licence to Springer Nature B.V.