Kinome Array Profiling of Patient-Derived Pancreatic Ductal Adenocarcinoma Identifies Differentially Active Protein Tyrosine Kinases.
Kinome Array Profiling of Patient-Derived Pancreatic Ductal Adenocarcinoma Identifies Differentially Active Protein Tyrosine Kinases.
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患者源性胰腺导管腺癌的Kinome阵列分析鉴定差异活性蛋白酪氨酸激酶。
DOI：
10.3390/ijms21228679
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发表时间：
2020-11-17
影响因子：
5.6
通讯作者：
McCullumsmith RE
中科院分区：
文献类型：
--
作者：
Creeden JF;Alganem K;Imami AS;Brunicardi FC;Liu SH;Shukla R;Tomar T;Naji F;McCullumsmith RE
胰腺癌仍然是最难治疗的恶性肿瘤之一。患者治疗效果的微小改善和患者生存率持续低迷凸显了对新治疗策略的巨大需求。目前，人们对针对酪氨酸蛋白激酶的治疗策略产生了浓厚的兴趣。在这里，我们采用了能够识别不同患者来源的胰腺导管腺癌 (PDAC) 细胞系和野生型胰腺组织中差异活性蛋白酪氨酸激酶的激酶组阵列和生物信息学管道，以研究 PDAC 样本的独特激酶组网络，并为胰腺癌治疗提出新的靶激酶。与之前描述的报告一致，基于肽的激酶组阵列谱鉴定出胰腺癌中以下激酶的蛋白酪氨酸激酶活性增加：表皮生长因子受体（EGFR）、fms相关受体酪氨酸激酶4/血管内皮生长因子受体3（FLT4/VEGFR-3）、胰岛素受体（INSR）、肝配蛋白受体A2（EPHA2）、血小板衍生生长因子受体α（PDGFRA）、SRC原癌基因激酶 (SRC) 和酪氨酸激酶非受体 2 (TNK2)。此外，这项研究发现蛋白酪氨酸激酶的活性增加，但先前证据表明胰腺癌中蛋白酪氨酸激酶的活性存在差异。这些蛋白酪氨酸激酶包括 B 淋巴样激酶 (BLK)、Fyn 相关激酶 (FRK)、Lck/Yes 相关新型激酶 (LYN)、FYN 原癌基因激酶 (FYN)、淋巴细胞特异性激酶 (LCK)、tec 蛋白激酶 (TEC)、造血细胞激酶 (HCK)、ABL 原癌基因 2 激酶 (ABL2)、盘状蛋白结构域受体 1 激酶(DDR1) 和肝配蛋白受体 A8 激酶 (EPHA8)。总之，这些结果支持肽阵列基因组分析在生成未来胰腺癌治疗开发的潜在候选激酶中的实用性。
Pancreatic cancer remains one of the most difficult malignancies to treat. Minimal improvements in patient outcomes and persistently abysmal patient survival rates underscore the great need for new treatment strategies. Currently, there is intense interest in therapeutic strategies that target tyrosine protein kinases. Here, we employed kinome arrays and bioinformatic pipelines capable of identifying differentially active protein tyrosine kinases in different patient-derived pancreatic ductal adenocarcinoma (PDAC) cell lines and wild-type pancreatic tissue to investigate the unique kinomic networks of PDAC samples and posit novel target kinases for pancreatic cancer therapy. Consistent with previously described reports, the resultant peptide-based kinome array profiles identified increased protein tyrosine kinase activity in pancreatic cancer for the following kinases: epidermal growth factor receptor (EGFR), fms related receptor tyrosine kinase 4/vascular endothelial growth factor receptor 3 (FLT4/VEGFR-3), insulin receptor (INSR), ephrin receptor A2 (EPHA2), platelet derived growth factor receptor alpha (PDGFRA), SRC proto-oncogene kinase (SRC), and tyrosine kinase non receptor 2 (TNK2). Furthermore, this study identified increased activity for protein tyrosine kinases with limited prior evidence of differential activity in pancreatic cancer. These protein tyrosine kinases include B lymphoid kinase (BLK), Fyn-related kinase (FRK), Lck/Yes-related novel kinase (LYN), FYN proto-oncogene kinase (FYN), lymphocyte cell-specific kinase (LCK), tec protein kinase (TEC), hemopoietic cell kinase (HCK), ABL proto-oncogene 2 kinase (ABL2), discoidin domain receptor 1 kinase (DDR1), and ephrin receptor A8 kinase (EPHA8). Together, these results support the utility of peptide array kinomic analyses in the generation of potential candidate kinases for future pancreatic cancer therapeutic development.
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影响因子：
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影响因子：
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通讯作者：
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