Department of Hepatobiliary and Pancreatic Surgery, The Third Xiangya Hospital, Central South University, Changsha, Hunan, 410013, PR China.
Department of Endocrinology, The Third Xiangya Hospital, Central South University, Changsha, Hunan, 410013, PR China.
Pancreatology. 2021 Apr;21(3):589-598. doi: 10.1016/j.pan.2021.01.011. Epub 2021 Jan 22.
S100 calcium binding protein A14 (S100A14) plays an important role in the progression of several types of cancer. However, its roles in pancreatic ductal adenocarcinoma (PDAC) are largely unexplored. Here, we characterized the functional roles of S100A14 in the progression and chemoresistance of PDAC. Gene expression microarray identified that S100A14 was significantly highly expressed in four pairs of human PDAC tumor compared with corresponding non-tumor tissues genes. Quantitative reverse transcription PCR (qRT-PCR), western blotting and immunohistochemical staining (IHC) showed that S100A14 was frequently overexpressed in PDAC cell lines and tissues. Moreover, expression level of S100A14 was positively correlated to advanced cancer stages. Further, Kaplan-Meier survival analysis suggested that PDAC patients with low S100A14 expression had longer overall survival in TCGA PDAC datasets. Transient overexpressing of S100A14 promoted cell proliferation, anchorage-independent colony formation, cell migration and invasion in cell lines with low endogenous S100A14 levels, while transient silencing of S100A14 inhibited cell proliferation, anchorage-independent colony formation, cell migration and invasion in cell lines with high endogenous S100A14 levels. Persistent knockdown of S100A14 by transducing shRNAs carrying lentivirus inhibited subcutaneous tumor formation in nude mice, and sensitized the PDAC cells to gemcitabine treatment. Taken together, S100A14 exhibited oncogenic properties by promoting cell proliferation, transformation, migration and invasion, and enhanced in vivo tumor growth. More importantly, inhibition of S100A14 could effectively abrogate the cancerous properties of the PDAC cells. Our study indicated that S100A14 was a valuable target for the development of therapeutic strategy, as well as a diagnostic and prognosis biomarker for PDAC patients.
S100 钙结合蛋白 A14（S100A14）在多种类型癌症的进展中发挥着重要作用。然而，其在胰腺导管腺癌（PDAC）中的作用在很大程度上尚未得到探索。在这里，我们描述了 S100A14 在 PDAC 进展和化学抗性中的功能作用。基因表达微阵列鉴定出，与相应的非肿瘤组织基因相比，S100A14 在四对人 PDAC 肿瘤中显著高表达。定量逆转录 PCR（qRT-PCR）、Western blot 和免疫组织化学染色（IHC）显示，S100A14 在 PDAC 细胞系和组织中频繁过表达。此外，S100A14 的表达水平与癌症晚期呈正相关。进一步，Kaplan-Meier 生存分析表明，TCGA PDAC 数据集中 S100A14 低表达的 PDAC 患者总生存期更长。瞬时过表达 S100A14 促进低内源性 S100A14 水平的细胞系中的细胞增殖、无锚定依赖性集落形成、细胞迁移和侵袭，而瞬时沉默 S100A14 抑制高内源性 S100A14 水平的细胞系中的细胞增殖、无锚定依赖性集落形成、细胞迁移和侵袭。通过转导携带慢病毒的 shRNA 持续敲低 S100A14 抑制裸鼠皮下肿瘤形成，并使 PDAC 细胞对吉西他滨治疗敏感。总之，S100A14 通过促进细胞增殖、转化、迁移和侵袭表现出致癌特性，并增强体内肿瘤生长。更重要的是，抑制 S100A14 可以有效消除 PDAC 细胞的癌变特性。我们的研究表明，S100A14 是开发治疗策略的有价值的靶点，也是 PDAC 患者的诊断和预后生物标志物。
