title: Autophagy defects suggested by low levels of autophagy activator MAP1S and high levels of autophagy inhibitor LRPPRC predict poor prognosis of prostate cancer patients.
abstract: MAP1S (originally named C19ORF5) is a widely distributed homolog of neuronal-specific MAP1A and MAP1B, and bridges autophagic components with microtubules and mitochondria to affect autophagosomal biogenesis and degradation. Mitochondrion-associated protein LRPPRC functions as an inhibitor for autophagy initiation to protect mitochondria from autophagy degradation. MAP1S and LRPPRC interact with each other and may collaboratively regulate autophagy although the underlying mechanism is yet unknown. Previously, we have reported that LRPPRC levels serve as a prognosis marker of patients with prostate adenocarcinomas (PCA), and that patients with high LRPPRC levels survive a shorter period after surgery than those with low levels of LRPPRC. MAP1S levels are elevated in diethylnitrosamine-induced hepatocelular carcinomas in wildtype mice and the exposed MAP1S-deficient mice develop more malignant hepatocellular carcinomas. We performed immunochemical analysis to evaluate the co-relationship among the levels of MAP1S, LRPPRC, P62, and γ-H2AX. Samples were collected from wildtype and prostate-specific PTEN-deficient mice, 111 patients with PCA who had been followed up for 10 years and 38 patients with benign prostate hyperplasia enrolled in hospitals in Guangzhou, China. The levels of MAP1S were generally elevated so the MAP1S-mediated autophagy was activated in PCA developed in either PTEN-deficient mice or patients than their respective benign tumors. The MAP1S levels among patients with PCA vary dramatically, and patients with low MAP1S levels survive a shorter period than those with high MAP1S levels. Levels of MAP1S in collaboration with levels of LRPPRC can serve as markers for prognosis of prostate cancer patients.
authors.affiliation: Department of Urology, The Fifth Affiliated Hospital of Guangzhou Medical University, Guangzhou, 510700, China.|Center for Cancer and Stem Cell Biology, Institute of Biosciences and Technology, Texas A&M Health Science Center, Houston, Texas, 77030.
authors.forename: Xianhan
authors.initials: X
authors.lastname: Jiang
authors.affiliation: Department of Urology, Guangdong Key Laboratory of Clinical Molecular Medicine and Diagnostics, Guangzhou First People's Hospital, Guangzhou Medical University, Guangzhou, 510180, China.
authors.forename: Weide
authors.initials: W
authors.lastname: Zhong
authors.affiliation: Department of Urology, The Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, China.
authors.forename: Hai
authors.initials: H
authors.lastname: Huang
authors.affiliation: Department of Urology, Guangdong Key Laboratory of Clinical Molecular Medicine and Diagnostics, Guangzhou First People's Hospital, Guangzhou Medical University, Guangzhou, 510180, China.
authors.forename: Huichan
authors.initials: H
authors.lastname: He
authors.affiliation: Department of Urology, Guangdong Key Laboratory of Clinical Molecular Medicine and Diagnostics, Guangzhou First People's Hospital, Guangzhou Medical University, Guangzhou, 510180, China.
authors.forename: Funeng
authors.initials: F
authors.lastname: Jiang
authors.affiliation: Department of Urology, Guangdong Key Laboratory of Clinical Molecular Medicine and Diagnostics, Guangzhou First People's Hospital, Guangzhou Medical University, Guangzhou, 510180, China.
authors.forename: Yanru
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Center for Cancer and Stem Cell Biology, Institute of Biosciences and Technology, Texas A&M Health Science Center, Houston, Texas, 77030.
authors.forename: Fei
authors.initials: F
authors.lastname: Yue
authors.affiliation: Center for Cancer and Stem Cell Biology, Institute of Biosciences and Technology, Texas A&M Health Science Center, Houston, Texas, 77030.
authors.forename: Jing
authors.initials: J
authors.lastname: Zou
authors.affiliation: Department of Urology, The Fifth Affiliated Hospital of Guangzhou Medical University, Guangzhou, 510700, China.
authors.forename: Xun
authors.initials: X
authors.lastname: Li
authors.affiliation: Department of Urology, The Fifth Affiliated Hospital of Guangzhou Medical University, Guangzhou, 510700, China.
authors.forename: Yongzhong
authors.initials: Y
authors.lastname: He
authors.affiliation: Center for Cancer and Stem Cell Biology, Institute of Biosciences and Technology, Texas A&M Health Science Center, Houston, Texas, 77030.
authors.forename: Pan
authors.initials: P
authors.lastname: You
authors.affiliation: Department of Urology, The Fifth Affiliated Hospital of Guangzhou Medical University, Guangzhou, 510700, China.
authors.forename: Weiqiang
authors.initials: W
authors.lastname: Yang
authors.affiliation: Department of Urology, The Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, China.
authors.forename: Yiming
authors.initials: Y
authors.lastname: Lai
authors.affiliation: Center for Cancer and Stem Cell Biology, Institute of Biosciences and Technology, Texas A&M Health Science Center, Houston, Texas, 77030.
authors.forename: Fen
authors.initials: F
authors.lastname: Wang
authors.affiliation: Center for Cancer and Stem Cell Biology, Institute of Biosciences and Technology, Texas A&M Health Science Center, Houston, Texas, 77030.
authors.forename: Leyuan
authors.initials: L
authors.lastname: Liu
mesh_terms: D000230:Adenocarcinoma / Q000378:metabolism / Q000473:pathology; D000368:Aged; D000818:Animals; D001343:Autophagy / Q000502:physiology*; D006657:Histones / Q000378:metabolism; D006801:Humans; D008297:Male; D051379:Mice; D008869:Microtubule-Associated Proteins / Q000378:metabolism*; D009363:Neoplasm Proteins / Q000378:metabolism*; D051059:PTEN Phosphohydrolase / Q000378:metabolism; D011379:Prognosis; D011471:Prostatic Neoplasms / Q000378:metabolism* / Q000473:pathology*; D016601:RNA-Binding Proteins / Q000378:metabolism
chemical_list: D006657:Histones; D008869:Microtubule-Associated Proteins; D009363:Neoplasm Proteins; D016601:RNA-Binding Proteins; D051059:PTEN Phosphohydrolase
keywords: DNA double strand break; P62; PTEN; benign prostatic hyperplasia; overall survival; prostatic intraepithelial neoplasia