Department of General Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
Department of Biliary-Pancreatic Surgery, Affiliated Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei Province, China.
Mol Cancer Res. 2020 May;18(5):685-697. doi: 10.1158/1541-7786.MCR-19-0718. Epub 2020 Feb 4.
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 and . 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.
胰腺癌是人类最致命的恶性肿瘤之一，部分原因是其易于转移。然而，胰腺癌转移的机制仍不清楚。氧化型低密度脂蛋白受体 1（OLR1）是一种识别多种配体（如氧化型低密度脂蛋白）的凝集素样清道夫受体，先前在心血管和代谢疾病中有所报道。OLR1 在胰腺癌中的作用和机制尚不清楚。在本研究中，我们发现 OLR1 在胰腺癌组织中的表达明显高于相邻正常组织，并且与整体生存率降低密切相关。OLR1 通过上调 c-Myc 表达促进 HMGA2 转录，从而促进胰腺癌细胞的增殖和转移。此外，与 OLR1-c-Myc-HMGA2 轴低表达的患者相比，OLR1-c-Myc-HMGA2 轴高表达的胰腺癌患者预后更差。意义：我们的研究结果表明，OLR1-c-Myc-HMGA2 轴促进了胰腺癌细胞的转移，可能成为胰腺癌患者潜在的治疗靶点和预后标志物。
