Increased podocalyxin (PODXL) expression has been associated with a subset of aggressive types of cancer. To the best of our knowledge, the effect of PODXL on astrocytoma cell invasion and survival against chemotherapy agent was investigated for the first time in the present study. Overexpression and knockdown of PODXL were respectively performed in SW1783 (grade III astrocytoma) and U-87 (grade IV astrocytoma; gliobalstoma) cells. PODXL overexpression in SW1783 cells significantly increased cell invasion, matrix metalloproteinase-9 (MMP-9) expression, cell survival against temozolomide-induced apoptotic stress, and phosphorylation of Akt at serine 473 (ser473), which was abolished by the selective phosphatidylinositol 3-kinase (PI3K) inhibitor LY294002 (LY). Knockdown of PODXL in U-87 cells significantly decreased cell invasion, MMP-9 expression, cell survival against temozolomide, and phosphorylation of Akt at serine 473 (ser473), which was further decreased by LY treatment. In conclusion, in the present study it was demonstrated that PODXL promotes astrocytoma cell invasion, potentially through the upregulation of MMP-9 expression in a PI3K-dependent manner. Additionally, PODXL was shown to promote astrocytoma cell survival against temozolomide-induced apoptotic stress by enhancing the activation of the PI3K/Akt survival signaling pathway. This study provides novel insights into the molecular mechanisms underlying astrocytoma progression, cell survival and chemoresistance, and suggests that PODXL may be a potential target for overcoming chemoresistance in astrocytomas.
Keywords: astrocytoma; cell survival; chemoresistance; glioblastoma; invasion; phosphatidy linositol 3-kinase/Akt pathway; podocalyxin; temozolomide.