OLR1 Promotes Pancreatic Cancer Metastasis via Increased c-Myc Expression and Transcription of HMGA2
OLR1 Promotes Pancreatic Cancer Metastasis via Increased c-Myc Expression and Transcription of HMGA2
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OLR1 通过增加 c-Myc 表达和 HMGA2 转录促进胰腺癌转移
DOI：
10.1158/1541-7786.mcr-19-0718
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发表时间：
2020-02
影响因子：
5.2
通讯作者：
Zhao Yupei
中科院分区：
文献类型：
--
作者：
Yang Gang;Xiong Guangbing;Feng Mengyu;Zhao Fangyu;Qiu Jiangdong;Liu Yueze;Cao Zhe;Wang Huanyu;Yang Jinshou;You Lei;Zheng Lianfang;Zhang Taiping;Zhao Yupei
胰腺癌是人类最致命的恶性肿瘤之一，部分原因是它有转移的倾向。然而，胰腺癌的转移机制尚不清楚。氧化低密度脂蛋白受体1(OLR1)是一种凝集素样的清道夫受体，可识别氧化低密度脂蛋白等多种配体，已有报道用于心血管和代谢性疾病。OLR1在胰腺癌中的作用和机制尚不清楚。在这项研究中，我们发现OLR1在胰腺癌组织中的表达显著高于癌旁正常组织，并与总体生存率的降低密切相关。OLR1在体内外均能促进胰腺癌细胞的增殖和转移。机制上，OLR1通过上调c-Myc表达促进HMGA2转录，从而促进胰腺癌细胞的转移。此外，OLR1-c-Myc-HMGA2轴高表达的胰腺癌患者预后比OLR1-c-Myc-HMGA2轴低表达的患者差。提示：OLR1-c-Myc-HMGA2轴促进胰腺癌细胞的转移，可能成为胰腺癌治疗的潜在靶点和预后标记物。
Pancreatic cancer is one of the most lethal human malignancies, partly because of its propensity for metastasis. However, the mechanisms of metastasis in pancreatic cancer remain unclear. Oxidized low-density lipoprotein receptor 1 (OLR1), a lectin-like scavenger receptor that recognizes several ligands, such as oxidized low-density lipoprotein, was previously reported in cardiovascular and metabolic diseases. The role and mechanism of OLR1 in pancreatic cancer is unclear. In this study, we found that OLR1 expression was significantly higher in pancreatic cancer tissues than that in adjacent normal tissues and closely associated with reduced overall survival. OLR1 promoted proliferation and metastasis of pancreatic cancer cells in vitro and in vivo. Mechanistically, OLR1 increased HMGA2 transcription by upregulating c-Myc expression to promote the metastasis of pancreatic cancer cells. In addition, patients with pancreatic cancer with high expression of OLR1–c-Myc–HMGA2 axis showed worse prognosis compared with patients with low expression of OLR1–c-Myc–HMGA2 axis. Implications: Our findings suggested that the OLR1–c-Myc–HMGA2 axis promotes metastasis of pancreatic cancer cells and may serve as potential therapeutic targets and prognosis markers for patients with pancreatic cancer.
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影响因子：
7.3
作者：
Gao J;Aksoy BA;Dogrusoz U;Dresdner G;Gross B;Sumer SO;Sun Y;Jacobsen A;Sinha R;Larsson E;Cerami E;Sander C;Schultz N
通讯作者：
Schultz N
DOI：
10.1891/9780826121646.0002
发表时间：
2018-09
期刊：
Cancer Rehabilitation
影响因子：
--
作者：
K. Miller;R. Siegel;R. Khan;A. Jemal
通讯作者：
K. Miller;R. Siegel;R. Khan;A. Jemal
影响因子：
4.6
作者：
Li C;Zhang J;Wu H;Li L;Yang C;Song S;Peng P;Shao M;Zhang M;Zhao J;Zhao R;Wu W;Ruan Y;Wang L;Gu J
通讯作者：
Gu J
DOI：
10.1145/3155287
发表时间：
2017-12
期刊：
ACM Transactions on Architecture and Code Optimization (TACO)
影响因子：
--
作者：
Ramyad Hadidi;Lifeng Nai;Hyojong Kim;Hyesoon Kim
通讯作者：
Ramyad Hadidi;Lifeng Nai;Hyojong Kim;Hyesoon Kim
影响因子：
15.9
作者：
Chui, PC;Guan, HP;Lazar, MA
通讯作者：
Lazar, MA