Sperm‑associated antigen 9 promotes astrocytoma cell invasion through the upregulation of podocalyxin

Jiang,Jiaode; Liu,Yunsheng; Fang,Wenhua; Liu,Feng

doi:10.3892/mmr.2014.2168

July-2014 Volume 10 Issue 1

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July-2014 Volume 10 Issue 1

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Article

Sperm‑associated antigen 9 promotes astrocytoma cell invasion through the upregulation of podocalyxin

Authors:
- Jiaode Jiang
- Yunsheng Liu
- Wenhua Fang
- Feng Liu
View Affiliations / Copyright

Affiliations: Department of Neurosurgery, The Third Xiangya Hospital, Hunan, P.R. China, Department of Neurosurgery, Xiangya Hospital, Central South University, Changsha, Hunan, P.R. China, Department of Neurosurgery, The First Affiliated Hospital, Fujian Medical University, Fuzhou, Fujian, P.R. China
Pages: 417-422
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Published online on: April 24, 2014

https://doi.org/10.3892/mmr.2014.2168
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Abstract

Podocalyxin (PODXL) has been found to increase the aggressive phenotype of a number of cancers, including astrocytoma. In addition, the progression of astrocytoma has been associated with sperm‑associated antigen 9 (SPAG9), a recently characterized oncoprotein. In the present study, the association between SPAG9 and PODXL in human astrocytoma invasion and the underlying mechanisms were investigated for the first time, to the best of our knowledge. Overexpression and knockdown of SPAG9 were performed in SW1783 (grade III astrocytoma) and U87 (grade IV astrocytoma; glioblastoma) cells, respectively. PODXL expression at both the mRNA and the protein level, as well as the PODXL gene promoter activity, were significantly increased and decreased in parallel with the overexpression and knockdown of SPAG9 in astrocytoma cells; these effects were blocked by the selective c‑Jun N‑terminal kinase (JNK) inhibitor SP600125 (5 µM) and restored by the JNK agonist anisomycin (25 ng/ml), respectively. SPAG9 overexpression significantly increased cell invasion and matrix metalloproteinase‑9 (MMP‑9) expression in SW1783 cells, and this effect was reversed by knockdown of PODXL. In U87 cells, knockdown of SPAG9 markedly decreased cell invasion and MMP‑9 expression, which was completely restored by overexpression of PODXL. In conclusion, it was demonstrated in the present study that SPAG9 upregulates PODXL expression in human astrocytoma cells at the PODXL gene promoter/transcriptional level through a JNK‑dependent mechanism and that PODXL is a critical mediator of the promoting effect of SPAG9 on astrocytoma cell invasion, possibly through upregulation of MMP‑9 expression. This study provides novel insights into the molecular mechanisms involved in astrocytoma invasion.

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Journals

International Journal of Molecular Medicine

International Journal of Oncology

Molecular Medicine Reports

Oncology Reports

Experimental and Therapeutic Medicine

Oncology Letters

Biomedical Reports

Molecular and Clinical Oncology

World Academy of Sciences Journal

International Journal of Functional Nutrition

International Journal of Epigenetics

Medicine International

Sperm‑associated antigen 9 promotes astrocytoma cell invasion through the upregulation of podocalyxin

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