Ouyang Liang, Zhang Lan, Fu Leilei, Liu Bo
a State Key Laboratory of Biotherapy and Cancer Center , West China Hospital, Sichuan University, and Collaborative Innovation Center of Biotherapy , Chengdu , China.
Autophagy. 2017 Apr 3;13(4):777-778. doi: 10.1080/15548627.2017.1283470. Epub 2017 Feb 6.
ULK1 (unc-51 like autophagy activating kinase 1) is well known to be required to initiate the macroautophagy/autophagy process, and thus activation of ULK1-modulating autophagy/autophagy-associated cell death (ACD) may be a possible therapeutic strategy in triple negative breast cancer (TNBC). Here, our integrated The Cancer Genome Atlas (TCGA) data set, tissue microarray-based analyses and multiple biologic evaluations together demonstrate a new small-molecule activator of ULK1 for better understanding of how ULK1, the mammalian homolog of yeast Atg1, as a potential drug target can regulate ACD by the ULK complex (ULK1-ATG13-RB1CC1/FIP200-ATG101), as well as other possible ULK1 interactors, including ATF3, RAD21 and CASP3/caspase3 in TNBC. Moreover, such new inspiring findings may help us discover that this activator of ULK1 (LYN-1604) with its anti-tumor activity and ACD-modulating mechanisms can be further exploited as a small-molecule candidate drug for future TNBC therapy.
众所周知，ULK1（unc-51样自噬激活激酶1）是启动巨自噬/自噬过程所必需的，因此激活ULK1调节自噬/自噬相关细胞死亡（ACD）可能是三阴性乳腺癌（TNBC）的一种潜在治疗策略。在此，我们整合了癌症基因组图谱（TCGA）数据集、基于组织芯片的分析以及多种生物学评估，共同证明了一种新型ULK1小分子激活剂，有助于更好地理解作为潜在药物靶点的酵母Atg1的哺乳动物同源物ULK1如何通过ULK复合物（ULK1-ATG13-RB1CC1/FIP200-ATG101）以及TNBC中其他可能的ULK1相互作用蛋白（包括ATF3、RAD21和CASP3/半胱天冬酶3）来调节ACD。此外，这些新的鼓舞人心的发现可能有助于我们发现这种具有抗肿瘤活性和ACD调节机制的ULK1激活剂（LYN-1604）可作为未来TNBC治疗的小分子候选药物进一步开发利用。
