title: Autophagy protects ovarian cancer-associated fibroblasts against oxidative stress.
abstract: RNA-Seq and gene set enrichment anylysis revealed that ovarian cancer associated fibroblasts (CAFs) are mitotically active compared with normal fibroblasts (NFs). Cellular senescence is observed in CAFs treated with H2O2 as shown by elevated SA-β-gal activity and p21 (WAF1/Cip1) protein levels. Reactive oxygen species (ROS) production and p21 (WAF1/Cip1) elevation may account for H2O2-induced CAFs cell cycle arrest in S phase. Blockage of autophagy can increase ROS production in CAFs, leading to cell cycle arrest in S phase, cell proliferation inhibition and enhanced sensitivity to H2O2-induced cell death. ROS scavenger NAC can reduce ROS production and thus restore cell viability. Lactate dehydrogenase A (LDHA), monocarboxylic acid transporter 4 (MCT4) and superoxide dismutase 2 (SOD2) were up-regulated in CAFs compared with NFs. There was relatively high lactate content in CAFs than in NFs. Blockage of autophagy decreased LDHA, MCT4 and SOD2 protein levels in CAFs that might enhance ROS production. Blockage of autophagy can sensitize CAFs to chemotherapeutic drug cisplatin, implicating that autophagy might possess clinical utility as an attractive target for ovarian cancer treatment in the future.
authors.affiliation: a International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiao Tong University , Shanghai , P. R. China.|b Institute of Embryo-Fetal Original Adult Disease Affiliated to Shanghai Jiao Tong University School of Medicine , Shanghai , P. R. China.
authors.forename: Qian
authors.initials: Q
authors.lastname: Wang
authors.affiliation: c Shanghai Institute of Biochemistry and Cell Biology, SIBS, Chinese Academy of Sciences , Shanghai , China.
authors.forename: Liang
authors.initials: L
authors.lastname: Xue
authors.affiliation: c Shanghai Institute of Biochemistry and Cell Biology, SIBS, Chinese Academy of Sciences , Shanghai , China.
authors.forename: Xiaoyu
authors.initials: X
authors.lastname: Zhang
authors.affiliation: a International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiao Tong University , Shanghai , P. R. China.
authors.forename: Shixia
authors.initials: S
authors.lastname: Bu
authors.affiliation: c Shanghai Institute of Biochemistry and Cell Biology, SIBS, Chinese Academy of Sciences , Shanghai , China.
authors.forename: Xueliang
authors.initials: X
authors.lastname: Zhu
authors.affiliation: a International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiao Tong University , Shanghai , P. R. China.
authors.forename: Dongmei
authors.initials: D
authors.lastname: Lai
mesh_terms: D000111:Acetylcysteine / Q000494:pharmacology; D000199:Actins / Q000378:metabolism; D001343:Autophagy / Q000187:drug effects*; D000071187:Autophagy-Related Protein 5 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D000072645:Cancer-Associated Fibroblasts / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000378:metabolism; D005260:Female; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D006861:Hydrogen Peroxide / Q000633:toxicity*; D007527:Isoenzymes / Q000378:metabolism; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D000080864:Lactate Dehydrogenase 5; D027501:Monocarboxylic Acid Transporters / Q000378:metabolism; D009124:Muscle Proteins / Q000378:metabolism; D010051:Ovarian Neoplasms / Q000378:metabolism / Q000473:pathology; D018384:Oxidative Stress / Q000187:drug effects*; D017382:Reactive Oxygen Species / Q000378:metabolism; D059807:S Phase Cell Cycle Checkpoints / Q000187:drug effects; D013482:Superoxide Dismutase / Q000378:metabolism; D000099156:Superoxide Dismutase 2
chemical_list: D000111:Acetylcysteine; D000199:Actins; D000071187:Autophagy-Related Protein 5; D050759:Cyclin-Dependent Kinase Inhibitor p21; D006861:Hydrogen Peroxide; D007527:Isoenzymes; D007770:L-Lactate Dehydrogenase; D000080864:Lactate Dehydrogenase 5; D027501:Monocarboxylic Acid Transporters; D009124:Muscle Proteins; D017382:Reactive Oxygen Species; D013482:Superoxide Dismutase; D000099156:Superoxide Dismutase 2; C541116:ACTA2 protein, human; C406962:SLC16A4 protein, human
keywords: CAFs; LDHA; MCT4; ROS; SOD2; autophagy; ovarian cancer; oxidative stress