title: SPOCK1 is upregulated in recurrent glioblastoma and contributes to metastasis and Temozolomide resistance.
abstract: OBJECTIVE
  Glioblastoma multiforme (GBM) is the most aggressive brain tumour type in humans. Its poor prognosis is largely attributed to its invasiveness and high rate of recurrence. Recurring GBM is commonly resistant to chemotherapeutic drugs, making it specially difficult to treat. Recent studies have revealed that matricellular glycoprotein SPOCK1 to be upregulated in several cancer types and to be specifically expressed in invasive GBM, but not in other types of non-invasive brain tumour, which prompted us to study the mechanism of action of SPOCK1 in invasion, recurrence and drug resistance of GBM cells.
  
  
  METHODS
  SPOCK1 expression in GBM tissues was evaluated using qPCR, Western blotting and immunohistochemical staining. Cell migration was tested by the wound healing method and cell invasion was assessed using transwell plates with Matrigel coating. Western blotting was performed for E-cadherin, vimentin, N-cadherin, p-Akt and Akt. Cell viability was examined using the MTT assay.
  
  
  RESULTS
  We found that the expression of SPOCK1 was significantly upregulated in recurrent GBM. We also demonstrated that SPOCK1 positively regulated migration, invasion and EMT process of GBM cells. Furthermore, SPOCK1 mediated TMZ resistance in GBM, as knockdown of SPOCK1 expression in TMZ-resistant GBM cells substantially sensitized these cells to TMZ.
  
  
  CONCLUSIONS
  SPOCK1 results were positive and it mediated TMZ resistance in GBM. In addition, SPOCK1 regulated invasion and TMZ resistance in GBM cells via the Akt signalling pathway.
authors.affiliation: School of Pharmacy, Mudanjiang Medical University, Mudanjiang, Heilongjiang Province, 157011, China.
authors.forename: Fengbo
authors.initials: F
authors.lastname: Yu
authors.affiliation: Department of Neurosurgery, The First Hospital of Jilin University, Changchun, Jilin Province, 130021, China.
authors.forename: Guihong
authors.initials: G
authors.lastname: Li
authors.affiliation: Department of Emergency, Hongqi hospital of Mudanjiang Medical University, Mudanjiang, Heilongjiang Province, 157011, China.
authors.forename: Junxia
authors.initials: J
authors.lastname: Gao
authors.affiliation: Department of Neurosurgery, The First Hospital of Jilin University, Changchun, Jilin Province, 130021, China.
authors.forename: Yuxue
authors.initials: Y
authors.lastname: Sun
authors.affiliation: Department of Neurosurgery, The First Hospital of Jilin University, Changchun, Jilin Province, 130021, China.
authors.forename: Pengfei
authors.initials: P
authors.lastname: Liu
authors.affiliation: Department of Neurosurgery, The First Hospital of Jilin University, Changchun, Jilin Province, 130021, China.
authors.forename: Haijun
authors.initials: H
authors.lastname: Gao
authors.affiliation: Department of Neurosurgery, The First Hospital of Jilin University, Changchun, Jilin Province, 130021, China.
authors.forename: Peiwen
authors.initials: P
authors.lastname: Li
authors.affiliation: Department of Neurosurgery, The First Hospital of Jilin University, Changchun, Jilin Province, 130021, China.
authors.forename: Ting
authors.initials: T
authors.lastname: Lei
authors.affiliation: Department of Neurosurgery, The First Hospital of Jilin University, Changchun, Jilin Province, 130021, China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Department of Neurosurgery, The First Hospital of Jilin University, Changchun, Jilin Province, 130021, China.
authors.forename: Ye
authors.initials: Y
authors.lastname: Cheng
authors.affiliation: Department of Orthopaedics, Changhai Hospital Affiliated to the Second Military Medical University, Shanghai, 200433, China.
authors.forename: Xiao
authors.initials: X
authors.lastname: Zhai
authors.affiliation: Department of Orthopaedic Surgery, Keck School of Medicine, University of Southern California, Los Angeles, California, 90033, USA.
authors.forename: Arash J
authors.initials: AJ
authors.lastname: Sayari
authors.affiliation: Department of Neurosurgery, The First Hospital of Jilin University, Changchun, Jilin Province, 130021, China.
authors.forename: Haiyan
authors.initials: H
authors.lastname: Huang
authors.affiliation: Department of Neurosurgery, Hongqi Hospital of Mudanjiang Medical University, Mudanjiang, Heilongjiang Province, 157011, China.
authors.forename: Qingchun
authors.initials: Q
authors.lastname: Mu
mesh_terms: D018906:Antineoplastic Agents, Alkylating / Q000627:therapeutic use*; D001932:Brain Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000473:pathology*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D003606:Dacarbazine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D058750:Epithelial-Mesenchymal Transition / Q000235:genetics; D005909:Glioblastoma / Q000188:drug therapy / Q000235:genetics / Q000473:pathology*; D006801:Humans; D009361:Neoplasm Invasiveness / Q000235:genetics; D009364:Neoplasm Recurrence, Local / Q000235:genetics / Q000473:pathology; D011509:Proteoglycans / Q000096:biosynthesis / Q000235:genetics*; D000077204:Temozolomide
chemical_list: D018906:Antineoplastic Agents, Alkylating; D011509:Proteoglycans; C504369:SPOCK1 protein, human; D003606:Dacarbazine; D000077204:Temozolomide