ULK1 phosphorylates Exo70 to suppress breast cancer metastasis
ULK1 phosphorylates Exo70 to suppress breast cancer metastasis
复制标题
ULK1磷酸化Exo70抑制乳腺癌转移
DOI：
10.1038/s41467-019-13923-7
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发表时间：
2020-01-08
影响因子：
16.6
通讯作者：
Hu, Tianhui
中科院分区：
文献类型：
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作者：
Mao, Liyuan;Zhan, Yan-yan;Hu, Tianhui
据报道，蛋白激酶ULK 1的表达增加与乳腺癌转移呈负相关。在这里，我们报告了ULK 1抑制人类乳腺癌细胞的迁移和侵袭。抑制作用通过Exo 70的直接磷酸化介导，Exo 70是外囊复合物的关键组分。ULK 1磷酸化抑制Exo 70同源寡聚化及其组装成外囊复合物，这是细胞侵入期间细胞突起形成和基质金属蛋白酶分泌所需的。然而，在生长因子刺激下，Exo 70被ERK 1/2磷酸化，这反过来又抑制了其被ULK 1磷酸化。总之，我们的研究确定了Exo 70作为抑制癌症转移的ULK 1的底物，并证明了在肿瘤细胞侵袭期间两种对抗性调节机制得到了很好的协调。
Increased expression of protein kinase ULK1 was reported to negatively correlate with breast cancer metastasis. Here we report that ULK1 suppresses the migration and invasion of human breast cancer cells. The suppressive effect is mediated through direct phosphorylation of Exo70, a key component of the exocyst complex. ULK1 phosphorylation inhibits Exo70 homo-oligomerization as well as its assembly to the exocyst complex, which are needed for cell protrusion formation and matrix metalloproteinases secretion during cell invasion. Reversely, upon growth factor stimulation, Exo70 is phosphorylated by ERK1/2, which in turn suppresses its phosphorylation by ULK1. Together, our study identifies Exo70 as a substrate of ULK1 that inhibits cancer metastasis, and demonstrates that two counteractive regulatory mechanisms are well orchestrated during tumor cell invasion.