title: SRPX2 Enhances the Epithelial-Mesenchymal Transition and Temozolomide Resistance in Glioblastoma Cells.
abstract: Glioblastoma (GBM) is the most common and most aggressive central nervous system tumor in adults. Due to GBM cell invasiveness and resistance to chemotherapy, current medical interventions are not satisfactory, and the prognosis for GBM is poor. It is necessary to investigate the underlying mechanism of GBM metastasis and drug resistance so that more effective treatments can be developed for GBM patients. sushi repeat-containing protein, X-linked 2 (SRPX2) is a prognostic biomarker in many different cancer cell lines and is associated with poor prognosis in cancer patients. SRPX2 overexpression promotes interactions between tumor and endothelial cells, leading to tumor progression and metastasis. We hypothesize that SRPX2 also contributes to GBM chemotherapy resistance and metastasis. Our results revealed that GBM tumor samples from 42 patients expressed higher levels of SRPX2 than the control normal brain tissue samples. High-SRPX2 expression levels are correlated with poor prognosis in those patients, as well as resistance to temozolomide in cultured GBM cells. Up-regulating SRPX2 expression in cultured GBM cell lines facilitated invasiveness and migration of GBM cells, while down-regulating SRPX2 through RNA interference was inhibitory. These results suggest that SRPX2 plays an important role in GBM metastasis. Epithelial to mesenchymal transition (EMT) is one of the processes that facilitate GBM metastasis and resistance to chemotherapy. EMT marker expression was decreased in SRPX2 down-regulated GBM cells, and MAPK signaling pathway marker expression was also decreased when SRPX2 is knocked down in GBM-cultured cells. Blocking the MAPK signaling pathway inhibited GBM metastasis but did not inhibit cell invasion and migration in SRPX2 down-regulated cells. Our results indicate that SRPX2 facilitates GBM metastasis by enhancing the EMT process via the MAPK signaling pathway.
authors.affiliation: Department of Neurosurgery, The Third Affiliated Hospital of Harbin Medical University, 150 Haping Road, Nangang District, Harbin, 150081, Heilongjiang, China.|Department of Neurosurgery, The General Hospital of Daqing Oil Field, 9 Zhongkang Road, Saertu District, Daqing, 163001, Heilongjiang, China.
authors.forename: Haitao
authors.initials: H
authors.lastname: Tang
authors.affiliation: Department of Neurosurgery, The Fourth Affiliated Hospital of Harbin Medical University, 37 Yiyuan Road, Nangang District, Harbin, 150001, Heilongjiang, China.
authors.forename: Jiaxin
authors.initials: J
authors.lastname: Zhao
authors.affiliation: Department of Medical Oncology, The General Hospital of Daqing Oil Field, 9 Zhongkang Road, Saertu District, Daqing, 163001, Heilongjiang, China.
authors.forename: Liangyu
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Department of Neurosurgery, The General Hospital of Daqing Oil Field, 9 Zhongkang Road, Saertu District, Daqing, 163001, Heilongjiang, China.
authors.forename: Jiang
authors.initials: J
authors.lastname: Zhao
authors.affiliation: Department of Medical Oncology, The General Hospital of Daqing Oil Field, 9 Zhongkang Road, Saertu District, Daqing, 163001, Heilongjiang, China.
authors.forename: Yongzhi
authors.initials: Y
authors.lastname: Zhuang
authors.affiliation: Department of Neurosurgery, The Third Affiliated Hospital of Harbin Medical University, 150 Haping Road, Nangang District, Harbin, 150081, Heilongjiang, China. liangpengdoctor97@126.com.
authors.forename: Peng
authors.initials: P
authors.lastname: Liang
mesh_terms: D001932:Brain Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D003606:Dacarbazine / Q000031:analogs & derivatives* / Q000494:pharmacology; D019008:Drug Resistance, Neoplasm; D058750:Epithelial-Mesenchymal Transition / Q000187:drug effects*; D005909:Glioblastoma / Q000175:diagnosis* / Q000188:drug therapy; D006801:Humans; D008565:Membrane Proteins; D009361:Neoplasm Invasiveness; D009363:Neoplasm Proteins; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D011379:Prognosis; D034622:RNA Interference; D000077204:Temozolomide
chemical_list: D008565:Membrane Proteins; D009363:Neoplasm Proteins; D009419:Nerve Tissue Proteins; C116881:SRPX2 protein, human; D003606:Dacarbazine; D000077204:Temozolomide
keywords: EMT; Glioblastoma; MAPK signaling pathway; SRPX2