title: DAB2IP regulates EMT and metastasis of prostate cancer through targeting PROX1 transcription and destabilizing HIF1α protein.
abstract: Prospero-related homeobox 1 (PROX1) is an essential regulator in lymphangiogenesis and has been implicated in both oncogenic and tumor-suppressive functions in many types of human cancers. However, the role of PROX1 in prostate cancer (PCa) remains poorly understood. In this study, based on different PCa cell lines and knockout mice, we showed that PROX1 could be suppressed by DAB2IP, a novel member of the Ras GTPase-activating protein family and a critical player in control of epithelial-mesenchymal transition (EMT) and PCa metastasis. Mechanistically, PROX1 overexpression in DAB2IP-deficient PCa cells could enhance the accumulation of HIF1α protein by inhibiting ubiquitin pathway and then consequently induce an EMT response, which is characterized by repression of E-cadherin, up-regulation of vimentin and matrix metallopeptidases (MMPs) and enhancement of cell migration. Together, our data provides a new insight into mechanism that DAB2IP regulates EMT and PCa metastasis, especially points out the potential roles of its downstream PROX1/HIF1α signaling in a unique non-skeletal metastasis of PCa.
authors.affiliation: Department of Urology, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, PR China.
authors.forename: Bin
authors.initials: B
authors.lastname: Wang
authors.affiliation: Department of Urology, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, PR China.
authors.forename: Jun
authors.initials: J
authors.lastname: Huang
authors.affiliation: Department of Urology, Shaanxi Provincial People's Hospital, Xi'an 710068, PR China.
authors.forename: Jiancheng
authors.initials: J
authors.lastname: Zhou
authors.affiliation: Department of Urology, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, PR China.
authors.forename: Ke
authors.initials: K
authors.lastname: Hui
authors.affiliation: Department of Urology, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, PR China.
authors.forename: Shan
authors.initials: S
authors.lastname: Xu
authors.affiliation: Department of Urology, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, PR China.
authors.forename: Jinhai
authors.initials: J
authors.lastname: Fan
authors.affiliation: Department of Urology, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, PR China.
authors.forename: Lei
authors.initials: L
authors.lastname: Li
authors.affiliation: Department of Urology, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, PR China.
authors.forename: Xinyang
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Urology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
authors.forename: Jer-Tsong
authors.initials: JT
authors.lastname: Hsieh
authors.affiliation: Department of Urology, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, PR China. Electronic address: dalinhe@yahoo.com.
authors.forename: Dalin
authors.initials: D
authors.lastname: He
authors.affiliation: Department of Urology, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, PR China. Electronic address: kaijie_wu@163.com.
authors.forename: Kaijie
authors.initials: K
authors.lastname: Wu
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D058750:Epithelial-Mesenchymal Transition / Q000235:genetics*; D004848:Epithelium / Q000378:metabolism / Q000473:pathology; D015972:Gene Expression Regulation, Neoplastic; D057809:HEK293 Cells; D018398:Homeodomain Proteins / Q000235:genetics*; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism*; D008297:Male; D051379:Mice; D008954:Models, Biological; D009362:Neoplasm Metastasis; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000473:pathology*; D055550:Protein Stability; D014158:Transcription, Genetic; D025521:Tumor Suppressor Proteins / Q000235:genetics*; D020703:ras GTPase-Activating Proteins / Q000172:deficiency / Q000378:metabolism*; D000098551:Prospero-Related Homeobox 1 Protein
chemical_list: C462952:DAB2IP protein, human; C561450:Dab2ip protein, mouse; D018398:Homeodomain Proteins; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D025521:Tumor Suppressor Proteins; D000098551:Prospero-Related Homeobox 1 Protein; D020703:ras GTPase-Activating Proteins
keywords: DAB2IP; EMT; HIF1α; Metastasis; PROX1; Prostate cancer