Open AccessSPOCK1 is upregulated in recurrent glioblastoma and contributes to metastasis and Temozolomide resistance
Author(s) -
Yu Fengbo,
Li Guihong,
Gao Junxia,
Sun Yuxue,
Liu Pengfei,
Gao Haijun,
Li Peiwen,
Lei Ting,
Chen Yong,
Cheng Ye,
Zhai Xiao,
Sayari Arash. J.,
Huang Haiyan,
Mu Qingchun
Publication year - 2016
Publication title -
cell proliferation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.647
H-Index - 74
eISSN - 1365-2184
pISSN - 0960-7722
DOI - 10.1111/cpr.12241
Subject(s) - cancer research , temozolomide , protein kinase b , viability assay , biology , vimentin , downregulation and upregulation , cell migration , gene knockdown , metastasis , cell growth , cell , pathology , cancer , immunohistochemistry , medicine , cell culture , signal transduction , immunology , glioma , microbiology and biotechnology , biochemistry , genetics , gene
Objectives 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. Materials and 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. Conclusion 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.