HDAC inhibitors induce proline dehydrogenase (POX) transcription and anti-apoptotic autophagy in triple negative breast cancer  

作　　者：Huan Fang Guangshi Du Qiuju Wu Rong Liu Ceshi Chen Jing Feng 

机构地区：[1]Medical College,Anhui University of Science and Technology,Huainan 232001,China [2]Anhui University of Science and Technology Affiliated Fengxian Hospital,Shanghai 201499,China [3]Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences and Yunnan Province,Kunming Institute of Zoology,Chinese Academy of Sciences,Kunming 650223,China [4]Department of Laboratory Medicine&Central Laboratory,Southern Medical University Affiliated Fengxian Hospital,Shanghai 201499,China [5]Shanghai University of Medicine&Health Sciences,Affiliated Sixth Peoples Hospital South Campus,Shanghai 201499,China

出　　处：《Acta Biochimica et Biophysica Sinica》2019年第10期1064-1070,共7页生物化学与生物物理学报（英文版）

基　　金：supported by the grants from the Strategic Priority Research Program of the Chinese Academy of Sciences(No.XDA16010405 to C.C.);the National Natural Science Foundation of China(Nos.81672624 to J.F.,81830087,1602221,and 31771516 to C.C.,and 81772847 to R.L.).

摘　　要：Triple-negative breast cancer(TNBC)is the most aggressive subtype of breast cancer w ith poor clinical outcom es and w itho ut effective targeted therapies.Numerous studies have suggested that HDAC inhibitors(TSA/SAHA)may be effective in TNBCs.Proline oxidase,also known as proline dehydrogenase(POX/PRODH),is a key enzyme in the proline m etabolism pathway and plays a vital role in tum origenesis.In this study,we found that HDAC inhibitors(TSA/SAHA)significantly increased POX expression and autophagy through activating AMPK.Depletion of POX decreased autophagy and increased apoptosis induced by HDAC inhibitors in TNBC cells.These results suggest that POX contributes to cell survival under chemotherapeutic stresses and might serve as a potential target for treatm ent of TNBC.

关 键 词：HDAC inhibitors POX AMPK AUTOPHAGY apoptosis TRIPLE-NEGATIVE breast cancer 

分 类 号：R73[医药卫生—肿瘤]