Department of Clinical Laboratory Medicine, Sapporo Medical University School of Medicine, South-1, West-16, Chuo-ku, Sapporo 060-8543, Japan.
Int J Oncol. 2011 Jul;39(1):33-40. doi: 10.3892/ijo.2011.1011. Epub 2011 Apr 18.
Receptor tyrosine kinase EphB2 and autophagic machinery are known as tumor suppressors; however, the connection remains to be elucidated. Here, we show the link between EphB2 and autophagy. Sesamin, a major lignan in sesame oil, induced autophagy in the human colon cancer cell lines HT29 and LS180, as shown by electron microscopy, as well as Western blotting and immunofluorescence imaging using an anti-LC3 antibody. Receptor tyrosine kinase array analysis revealed that sesamin treatment increased the levels of unphosphorylated -EphA1 and -EphB2 in HT29 cells. Silencing of EphA1 and EphB2 blocked sesamin-induced autophagy as well as sesamin-induced loss of cell viability. These results show that EphA1 and EphB2 play a critical role in this process. The present study reveals a novel function for EphA1 and EphB2 in the induction of autophagy, suggesting a tumor suppressor role for these proteins in colorectal cancer.
受体酪氨酸激酶 EphB2 和自噬机制被认为是肿瘤抑制因子；然而，它们之间的联系仍有待阐明。在这里，我们展示了 EphB2 和自噬之间的联系。芝麻素是芝麻油中的一种主要木脂素，电子显微镜显示，它能诱导人结肠癌细胞系 HT29 和 LS180 发生自噬，同时Western blot 和使用 LC3 抗体的免疫荧光成像也显示了这一点。受体酪氨酸激酶阵列分析显示，芝麻素处理能增加 HT29 细胞中未磷酸化的 EphA1 和 EphB2 的水平。EphA1 和 EphB2 的沉默阻断了芝麻素诱导的自噬以及芝麻素诱导的细胞活力丧失。这些结果表明 EphA1 和 EphB2 在这个过程中起着关键作用。本研究揭示了 EphA1 和 EphB2 在诱导自噬中的新功能，提示这些蛋白在结直肠癌中发挥肿瘤抑制作用。
