title: CD54-NOTCH1 axis controls tumor initiation and cancer stem cell functions in human prostate cancer.
abstract: Cancer stem cells (CSCs) are considered one of the key contributors to chemoresistance and tumor recurrence. Therefore, the precise identification of reliable CSC markers and clarification of the intracellular signaling involved in CSCs remains a great challenge in fields relating to cancer biology. Here, we implemented a novel chemoresistant prostate cancer patient-derived xenograft (PDX) model in NOD/SCID mice and identified CD54 as a candidate gene among the most highly enriched gene expression profiles in prostate tumors exposed to chronic cisplatin administration. Additionalin vitroandin vivoassays showed that CD54 played a critical role in the self-renewal and tumorigenesis of prostate CSCs. Moreover, silencing CD54 greatly reduced the tumorigenesis of prostate cancers bothin vitroandin vivoand significantly extended the survival time of tumor-bearing mice in a prostate cancer xenograft model. Dissection of the molecular mechanism revealed that the p38-Notch1 axis was the main downstream signaling pathway in CD54-mediated regulation of CSCs in prostate cancers. Together, these results established that CD54 could be a novel reliable prostate CSC marker and provided a new potential therapeutic target in prostate cancer via CD54-Notch1 signaling.
authors.affiliation: Core Facility for Protein Research, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China.; Beijing Jianlan Institute of Medicine, Beijing 100190, China.
authors.forename: Chong
authors.initials: C
authors.lastname: Li
authors.affiliation: Department of Medicine, Harvard Medical School, Boston, MA 02115, USA.; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA.
authors.forename: Shengwu
authors.initials: S
authors.lastname: Liu
authors.affiliation: Department of Urology, The Second Affiliated Hospital of Kunming Medical College, Kunming 650101, China.
authors.forename: Ruping
authors.initials: R
authors.lastname: Yan
authors.affiliation: Department of Life Science and Technology, China Pharmaceutical University, Nanjing 211198, China.
authors.forename: Ning
authors.initials: N
authors.lastname: Han
authors.affiliation: Department of Medicine, Harvard Medical School, Boston, MA 02115, USA.; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA.
authors.forename: Kwok-Kin
authors.initials: KK
authors.lastname: Wong
authors.affiliation: Department of Urology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Li
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D004195:Disease Models, Animal; D020869:Gene Expression Profiling; D020868:Gene Silencing; D064593:Heterografts; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism*; D008297:Male; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D014411:Neoplastic Stem Cells / Q000378:metabolism*; D011471:Prostatic Neoplasms / Q000503:physiopathology*; D051881:Receptor, Notch1 / Q000378:metabolism*; D016019:Survival Analysis
chemical_list: C497761:NOTCH1 protein, human; D051881:Receptor, Notch1; D018799:Intercellular Adhesion Molecule-1
keywords: CD54; NOTCH1.; cancer stem cells; prostate cancer