A small-molecule activator induces ULK1-modulating autophagy-associated cell death in triple negative breast cancer.
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.
a State Key Laboratory of Biotherapy and Cancer Center , West China Hospital, Sichuan University, and Collaborative Innovation Center of Biotherapy , Chengdu , China.
Liang
L
Ouyang
a State Key Laboratory of Biotherapy and Cancer Center , West China Hospital, Sichuan University, and Collaborative Innovation Center of Biotherapy , Chengdu , China.
Lan
L
Zhang
a State Key Laboratory of Biotherapy and Cancer Center , West China Hospital, Sichuan University, and Collaborative Innovation Center of Biotherapy , Chengdu , China.
Leilei
L
Fu
a State Key Laboratory of Biotherapy and Cancer Center , West China Hospital, Sichuan University, and Collaborative Innovation Center of Biotherapy , Chengdu , China.
Bo
B
Liu
D017209:Apoptosis / Q000187:drug effects*; D001343:Autophagy / Q000187:drug effects*; D000071189:Autophagy-Related Protein-1 Homolog / Q000378:metabolism*; D006801:Humans; D008954:Models, Biological; D054852:Small Molecule Libraries / Q000737:chemistry / Q000494:pharmacology*; D064726:Triple Negative Breast Neoplasms / Q000201:enzymology* / Q000473:pathology*
D054852:Small Molecule Libraries; D000071189:Autophagy-Related Protein-1 Homolog
ULK1 activator; UNC-51-like kinase 1 (ULK1); autophagy; autophagy-associated cell death (ACD); triple negative breast cancer (TNBC)