Sato Younosuke, Matsuo Akira, Kudoh Shinji, Fang Liu, Hasegawa Koki, Shinmyo Yohei, Ito Takaaki
Department of Pathology and Experimental Medicine, Graduate School of Medical Sciences, Kumamoto University, Honjo 1-1-1, Chuo-ku, Kumamoto 860-8556, Japan.
Department of Clinical Laboratory, Fourth Affiliated Hospital of Harbin Medical University, Harbin, China.
Acta Histochem Cytochem. 2018 Feb 27;51(1):53-62. doi: 10.1267/ahc.17035. Epub 2018 Feb 21.
Guidance molecules, such as Netrin-1, and their receptors have important roles in controlling axon pathfinding, modulate biological activities of various cancer cells, and may be a useful target for cancer therapy. Dorsal repulsive axon guidance protein (Draxin) is a novel guidance molecule that binds not only common guidance molecule receptors with Netrin-1, but also directly binds the EGF domain of Netrin-1 through a 22-amino-acid peptide (22aa). By immunostaining, Draxin was positively expressed in small cell carcinoma, adenocarcinoma (ADC), and squamous cell carcinoma of the lung. In addition, western blot analysis revealed that Draxin was expressed in all histological types of lung cancer cell lines examined. Knockdown of Draxin in an ADC cell line H358 resulted in altered expression of molecules associated with proliferation and apoptosis. The Ki-67 labeling index of Draxin-knockdown ADC cells was increased compared to that of control ADC cells. In H358 cells, treatment of 22aa induced phosphorylation of histone H3, but did not change apoptosis-associated enzymes. These data suggest that Draxin might be involved in cell proliferation and apoptosis in lung adenocarcinoma cells.
导向分子，如Netrin-1，及其受体在控制轴突导向、调节各种癌细胞的生物学活性方面发挥着重要作用，可能是癌症治疗的一个有用靶点。背侧排斥轴突导向蛋白（Draxin）是一种新型导向分子，它不仅与Netrin-1的常见导向分子受体结合，还通过一个22个氨基酸的肽段（22aa）直接结合Netrin-1的EGF结构域。通过免疫染色，Draxin在肺小细胞癌、腺癌（ADC）和肺鳞状细胞癌中呈阳性表达。此外，蛋白质印迹分析显示，Draxin在所检测的所有组织学类型的肺癌细胞系中均有表达。在ADC细胞系H358中敲低Draxin导致与增殖和凋亡相关分子的表达发生改变。与对照ADC细胞相比，敲低Draxin的ADC细胞的Ki-67标记指数增加。在H358细胞中，用22aa处理可诱导组蛋白H3磷酸化，但不改变凋亡相关酶。这些数据表明，Draxin可能参与肺腺癌细胞的细胞增殖和凋亡。
