Yoon Jong Hyuk, Kim Dayea, Kim Jaeyoon, Lee Hyeongjoo, Ghim Jaewang, Kang Byung Jun, Song Parkyong, Suh Pann-Ghill, Ryu Sung Ho, Lee Taehoon G
Department of Neural Development and Disease, Korea Brain Research Institute, Daegu, Republic of Korea
New Drug Development Center, Daegu-Gyeongbuk Medical Innovation Foundation, Daegu, Republic of Korea.
Cancer Genomics Proteomics. 2018 Nov-Dec;15(6):485-497. doi: 10.21873/cgp.20107.
There are limitations to current colorectal cancer (CRC)-specific diagnostic methods and therapies. Tumorigenesis proceeds because of interaction between cancer cells and various surrounding cells; discovering new molecular mediators through studies of the CRC secretome is a promising approach for the development of CRC diagnostics and therapies.
A comparative secretomic analysis was performed using primary and metastatic human isogenic CRC cells. Proliferation was determined by MTT and thymidine incorporation assay, migration was determined by wound-healing assay (ELISA). The level of palmitoleoyl-protein carboxylesterase (NOTUM) in plasma from patients with CRC was determined by enzyme-linked immunosorbent assay.
NOTUM expression was increased in metastatic cells. Proliferation was suppressed by inhibiting expression of NOTUM. Knockdown of NOTUM genes inhibited proliferation as well as migration, with possible involvement of p38 and c-JUN N-terminal kinase in this process. The result was verified in patients with CRC.
NOTUM may be a new candidate for diagnostics and therapy of CRC.
目前的结直肠癌（CRC）特异性诊断方法和治疗方法存在局限性。肿瘤发生是由于癌细胞与周围各种细胞之间的相互作用；通过对CRC分泌组的研究发现新的分子介质是开发CRC诊断和治疗方法的一种有前途的途径。
使用原发性和转移性人同基因CRC细胞进行比较分泌组分析。通过MTT和胸腺嘧啶掺入试验测定增殖，通过伤口愈合试验（ELISA）测定迁移。通过酶联免疫吸附测定法测定CRC患者血浆中棕榈油酰蛋白羧基酯酶（NOTUM）的水平。
NOTUM在转移细胞中的表达增加。抑制NOTUM的表达可抑制增殖。敲低NOTUM基因可抑制增殖和迁移，此过程中p38和c-JUN N末端激酶可能参与其中。该结果在CRC患者中得到验证。
NOTUM可能是CRC诊断和治疗的新候选物。
