FASTKD2 promotes cancer cell progression through upregulating Myc expression in pancreatic ductal adenocarcinoma
FASTKD2 promotes cancer cell progression through upregulating Myc expression in pancreatic ductal adenocarcinoma
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FASTKD2 通过上调胰腺导管腺癌中 Myc 表达促进癌细胞进展
DOI：
10.1002/jcb.29468
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发表时间：
2019-11-06
影响因子：
4
通讯作者：
Liu, Tao
中科院分区：
文献类型：
--
作者：
Fang, Rui;Zhang, Bin;Liu, Tao
胰腺导管腺癌（PDAC）是消化系统最致命的癌症之一。尽管发展了新的治疗方法，包括化疗、放疗和分子靶向治疗，但PDAC的发病率几乎等于死亡率，5年总生存率低于5%。在95%的PDAC患者标本中发现了Kras突变，但在临床前试验中，靶向Kras突变并未使胰腺癌患者受益。c‐Myc是Kras信号通路的主要效应分子之一。在这项研究中，我们发现FAST激酶结构域蛋白2 （FASTKD2）的失调导致PDAC患者预后不良。然后，我们发现FASTKD2促进胰腺癌细胞的增殖和侵袭。重要的是，我们证明了c‐Myc通过FASTKD2/BRD4轴转录增加，并负责FASTKD2介导的胰腺癌细胞的肿瘤生长和侵袭。总的来说，这项研究揭示了FASTKD2通过上调胰腺癌中Myc的表达来促进癌细胞的进展。FASTKD2可能是胰腺癌治疗的潜在靶点。
Pancreatic ductal adenocarcinoma (PDAC) is one of the most fatal cancers of the digestive system. Despite the development of novel therapeutic methods, including chemotherapy, radiotherapy, and molecular targeted therapy, the incidence rate of PDAC is almost equal to the mortality rate with 5‐year overall survival rate less than 5%. Kras mutation is found in 95% of patient with PDAC specimens, but targeting Kras mutation do not benefit patients with pancreatic cancer in preclinical trials. c‐Myc is one of the main effector molecules of the Kras signaling pathway. In this study, we found that dysregulation of FAST kinase–domain‐containing protein 2 (FASTKD2) resulted in the poor prognosis of patients with PDAC. Then, we showed that FASTKD2 promoted pancreatic cancer cell proliferation and invasion. Importantly, we demonstrated that c‐Myc was transcriptionally increased by FASTKD2/BRD4 axis and responsible for FASTKD2‐mediated tumor growth and invasion in pancreatic cancer cells. Collectively, this study uncovered that FASTKD2 promoted cancer cell progression through upregulating Myc expression in pancreatic cancer. FASTKD2 might be a potential target for pancreatic cancer therapy.