Increased Nuclear Transporter KPNA2 Contributes to Tumor Immune Evasion by Enhancing PD-L1 Expression in PDAC.
Increased Nuclear Transporter KPNA2 Contributes to Tumor Immune Evasion by Enhancing PD-L1 Expression in PDAC.
复制标题
核转运蛋白 KPNA2 的增加通过增强 PDAC 中的 PD-L1 表达来促进肿瘤免疫逃避
DOI：
10.1155/2021/6694392
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发表时间：
2021
影响因子：
4.1
通讯作者：
Zhang ZG
中科院分区：
文献类型：
--
作者：
Zhou KX;Huang S;Hu LP;Zhang XL;Qin WT;Zhang YL;Yao LL;Yu Y;Zhou YQ;Zhu L;Ji J;Zhang ZG
胰腺导管腺癌（PDAC）是最致命的恶性肿瘤之一，并以其对治疗的高抗性和低反应而闻名。肿瘤免疫逃避是设计有效抗癌治疗策略的主要绊脚石。核转运蛋白α 2（KPNA 2）是核转运蛋白家族的一员，在多种人类癌症中升高并加速癌变。然而，KPNA 2在PDAC中的具体作用仍不清楚。在这项研究中，我们发现，与邻近的非肿瘤组织相比，PDAC中KPNA 2的表达显著上调，并且通过分析GEO数据集，其高表达与不良生存结局相关。通过IHC染色，在人类患者样本和KPC小鼠模型中也发现了相似的KPNA 2表达模式。虽然KPNA 2敲低在体外未能损害PDAC细胞的活力和迁移能力，但通过沉默KPNA 2，体内肿瘤生长显著受阻，免疫检查点配体PD-L1的表达降低。此外，我们发现KPNA 2通过介导STAT 3的核转位来调节PD-L1的表达。总的来说，我们的数据表明，KPNA 2有潜力作为一个有前途的生物标志物诊断PDAC。
Pancreatic ductal adenocarcinoma (PDAC) is one of the deadliest malignancies and is known for its high resistance and low response to treatment. Tumor immune evasion is a major stumbling block in designing effective anticancer therapeutic strategies. Karyopherin alpha 2 (KPNA2), a member of the nuclear transporter family, is elevated in multiple human cancers and accelerates carcinogenesis. However, the specific role of KPNA2 in PDAC remains unclear. In this study, we found that expression of KPNA2 was significantly upregulated in PDAC compared to adjacent nontumor tissue and its high expression was correlated with poor survival outcome by analyzing the GEO datasets. Similar KPNA2 expression pattern was also found in both human patient samples and KPC mouse models through IHC staining. Although KPNA2 knockdown failed to impair the vitality and migration ability of PDAC cells in vitro, the in vivo tumor growth was significantly impeded and the expression of immune checkpoint ligand PD-L1 was reduced by silencing KPNA2. Furthermore, we uncovered that KPNA2 modulated the expression of PD-L1 by mediating nuclear translocation of STAT3. Collectively, our data suggested that KPNA2 has the potential to serve as a promising biomarker for diagnosis in PDAC.
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影响因子：
254.7
作者：
Jemal, Ahmedin;Siegel, Rebecca;Thun, Michael J.
通讯作者：
Thun, Michael J.
影响因子：
50.3
作者：
Bear AS;Vonderheide RH;O'Hara MH
通讯作者：
O'Hara MH
影响因子：
3.6
作者：
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通讯作者：
Shirabe, Ken
DOI：
10.1186/s13046-020-01687-8
发表时间：
2020-09-05
影响因子：
11.3
作者：
Zhang, Hao;Zhu, Changhao;Sun, Chengyi
通讯作者：
Sun, Chengyi
影响因子：
37.3
作者：
Ren B;Cui M;Yang G;Wang H;Feng M;You L;Zhao Y
通讯作者：
Zhao Y