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Securin promotes migration and invasion via matrix metalloproteinases in glioma cells.

ABSTRACT: Human securin, encoded by pituitary tumor transforming gene 1, is implicated in several oncogenic processes in the pathogenesis of brain tumors, including glioma. The aim of the present study was to examine the effect of securin on the migration and invasion of glioma cells. The results revealed that the overexpression of securin in glioma LN-229 cells significantly increased the invasion and transmigration abilities. By contrast, these abilities were significantly reduced by the downregulation of securin in glioma U373 cells. Furthermore, the results demonstrated that securin overexpression and downregulation significantly increased and decreased the levels of matrix metalloproteinase 2 and 9, respectively. These findings indicate a promotive role for securin in glioma migration and invasion, which may involve the action of matrix metalloproteinases.

SUBMITTER: Yan H

PROVIDER: S-EPMC4473712 | biostudies-literature | 2015 Jun

REPOSITORIES: biostudies-literature

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Securin promotes migration and invasion via matrix metalloproteinases in glioma cells.

Yan Haicheng H Wang Wei W Dou Changwu C Tian Fuming F Qi Songtao S

Oncology letters 20150326 6

Human securin, encoded by pituitary tumor transforming gene 1, is implicated in several oncogenic processes in the pathogenesis of brain tumors, including glioma. The aim of the present study was to examine the effect of securin on the migration and invasion of glioma cells. The results revealed that the overexpression of securin in glioma LN-229 cells significantly increased the invasion and transmigration abilities. By contrast, these abilities were significantly reduced by the downregulation ...[more]

PMID: 26137166

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Project description:Background: Accumulating evidence indicates that aberrant activation of the Hedgehog (Hh) signalling pathway by Glioma-associated oncogene (Gli) transcription factors is involved in the aggressive progression of cancers, including ovarian cancer. Whereas the molecular mechanism underlying this phenomenon remains unelucidated. Matrix metalloproteinase-7 (MMP-7) facilitates degradation of the extracellular matrix, promoting the invasion of tumour cells, and is associated with cancer progression and metastasis. In previous reports, we identified a set of genes regulated by Hh signalling in ovarian tumour cells among which MMP-7 was identified as a potential Hh target gene candidate. However, establishing an association between Hh signalling activation and MMP-7 expression requires further validation, and the function of this regulation remains unknown. Methods: A cDNA microarray was utilized to identify potential downstream targets of Hh signalling. Quantitative reverse transcription polymerase chain reaction (qRT-PCR) was used to evaluate mRNA expression, and immunoblotting (IB) was conducted to evaluate protein expression. The invasive and migratory capabilities of tumour cells were tested with the transwell and wound healing assays, respectively. The mRNA levels of Gli2 and MMP-7 in normal ovarian tissues and cancerous tissues in various stages together with the corresponding clinical information were acquired from the indicated GEO datasets to elucidate associations between MMP-7 expression and cancer progression and prognosis. Additionally, immunohistochemistry (IHC) was performed in multiple ovarian cancers, benign tumours and normal tissues to evaluate Gli2 and MMP-7 protein expression. Results: MMP-7 expression was regulated by the Hh ligand, antagonist and downstream transcript factor Gli2, demonstrating this gene as an Hh target. MMP-7 facilitated the invasion and migration of ovarian tumour cells, indicating its key function in ovarian cancer progression. IHC analysis demonstrated abnormally increased Gli2 and MMP-7 expression levels in benign tumours and ovarian cancer tissues. Moreover, high MMP-7 levels were significantly associated with poor overall survival (OS) and poor progression-free survival (PFS) in ovarian cancer patients. Conclusion: Aberrant activation of the Hh-Gli-MMP-7 signalling axis is essential for acceleration of the progression and metastasis of human ovarian cancer, implicating its use as a novel therapeutic target of ovarian cancer. In addition, MMP-7 can potentially serve as a prognostic marker of ovarian cancer.

Dataset Information

Securin promotes migration and invasion via matrix metalloproteinases in glioma cells.

Publications

Securin promotes migration and invasion via matrix metalloproteinases in glioma cells.

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