State Key Laboratory of Cancer Biology and Institute of Digestive Diseases, Xijing Hospital of Digestive Disease, Fourth Military Medical University, Xi'an 710032, PR China.
Biochem Biophys Res Commun. 2011 Jan 21;404(3):802-8. doi: 10.1016/j.bbrc.2010.12.063. Epub 2010 Dec 17.
KAI1, a metastasis-suppressor gene belonging to the tetraspanin family, is known to inhibit cancer metastasis without affecting the primary tumorigenicity by inhibiting the epidermal growth factor (EGF) signaling pathway. Recent studies have shown that hypoxic conditions of solid tumors induce high-level autophagy and KAI1 expression. However, the relationship between autophagy and KAI1 remains unclear. By using transmission electron microscopy, confocal microscopy, and Western blotting, we found that KAI1 can induce autophagy in a dose- and time-dependent manner in the human pancreatic cell line MiaPaCa-2. KAI1-induced autophagy was confirmed by the expression of autophagy-related proteins LC3 and Beclin 1. KAI1 induces autophagy through phosphorylation of extracellular signal-related kinases rather than that of AKT. KAI1-induced autophagy protects MiaPaCa-2 cells from apoptosis and proliferation inhibition partially through the downregulation of poly [adenosine diphosphate (ADP)-ribose] polymerase (PARP) cleavage and caspase-3 activation.
KAI1 是一种属于四跨膜蛋白家族的转移抑制基因，通过抑制表皮生长因子（EGF）信号通路，已知其能抑制癌症转移而不影响原肿瘤发生能力。最近的研究表明，实体瘤的缺氧条件诱导高水平自噬和 KAI1 表达。然而，自噬与 KAI1 之间的关系尚不清楚。通过使用透射电子显微镜、共聚焦显微镜和 Western blot，我们发现 KAI1 可在人胰腺细胞系 MiaPaCa-2 中以剂量和时间依赖的方式诱导自噬。自噬相关蛋白 LC3 和 Beclin 1 的表达证实了 KAI1 诱导的自噬。KAI1 通过细胞外信号相关激酶的磷酸化而不是 AKT 的磷酸化诱导自噬。KAI1 诱导的自噬通过下调多聚（腺嘌呤二磷酸核糖）聚合酶（PARP）裂解和半胱天冬酶-3 激活，部分保护 MiaPaCa-2 细胞免于凋亡和增殖抑制。
