NUPR1 maintains autolysosomal efflux by activating SNAP25 transcription in cancer cells
NUPR1 maintains autolysosomal efflux by activating SNAP25 transcription in cancer cells
复制标题
Nupr1 通过激活癌细胞中的 SNAP-25 转录来维持自体溶酶体流出
DOI：
10.1080/15548627.2017.1338556
复制
发表时间：
2018-01-01
期刊：
影响因子：
13.3
通讯作者：
Liu, Zhe
中科院分区：
文献类型：
--
作者：
Mu, Yanchao;Yan, Xiaojie;Liu, Zhe
在癌症晚期，自噬被认为可通过其缓解各种细胞应激的能力促进肿瘤进展。然而，在这类肿瘤中自噬如何受到稳态调节的细节尚不清楚。在此，我们报道一种转录辅调节因子NUPR1（核蛋白1，转录调节因子）在一部分癌细胞中异常表达，并且预示着肺癌患者的总体生存率较低。NUPR1通过诱导SNARE蛋白SNAP25调节自噬溶酶体加工的后期阶段，SNAP25与溶酶体SNARE相关蛋白VAMP8形成复合物。NUPR1的缺失会使自噬通量失调并损害自噬溶酶体的清除，在体外诱导大量细胞质空泡化和过早衰老，在体内抑制肿瘤。总之，我们的数据表明NUPR1是自噬溶酶体动力学的一种强效调节因子，并且是一些上皮癌进展所必需的。
ABSTRACT In the advanced stages of cancer, autophagy is thought to promote tumor progression through its ability to mitigate various cellular stresses. However, the details of how autophagy is homeostatically regulated in such tumors are unknown. Here, we report that NUPR1 (nuclear protein 1, transcriptional regulator), a transcriptional coregulator, is aberrantly expressed in a subset of cancer cells and predicts low overall survival rates for lung cancer patients. NUPR1 regulates the late stages of autolysosome processing through the induction of the SNARE protein SNAP25, which forms a complex with the lysosomal SNARE-associated protein VAMP8. NUPR1 depletion deregulates autophagic flux and impairs autolysosomal clearance, inducing massive cytoplasmic vacuolization and premature senescence in vitro and tumor suppression in vivo. Collectively, our data show that NUPR1 is a potent regulator of autolysosomal dynamics and is required for the progression of some epithelial cancers.