Allopregnanolone Promotes Migration and Invasion of Human Glioblastoma Cells through the Protein Tyrosine Kinase c-Src Activation
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES(2022)
Abstract
Glioblastomas (GBs) are the most aggressive and common primary malignant brain tumors. Steroid hormone progesterone (P4) and its neuroactive metabolites, such as allopregnanolone (3 alpha-THP) are synthesized by neural, glial, and malignant GB cells. P4 promotes cellular proliferation, migration, and invasion of human GB cells at physiological concentrations. It has been reported that 3 alpha-THP promotes GB cell proliferation. Here we investigated the effects of 3 alpha-THP on GB cell migration and invasion, the participation of the enzymes involved in its metabolism (AKR1C1-4), and the role of the c-Src kinase in 3 alpha-THP effects in GBs. 3 alpha-THP 100 nM promoted migration and invasion of U251, U87, and LN229 human-derived GB cell lines. We observed that U251, LN229, and T98G cell lines exhibited a higher protein content of AKR1C1-4 than normal human astrocytes. AKR1C1-4 silencing did not modify 3 alpha-THP effects on migration and invasion. 3 alpha-THP activated c-Src protein at 10 min (U251 cells) and 15 min (U87 and LN229 cells). Interestingly, the pharmacological inhibition of c-Src decreases the promoting effects of 3 alpha-THP on cell migration and invasion. Together, these data indicate that 3 alpha-THP promotes GB migration and invasion through c-Src activation.
MoreTranslated text
Key words
allopregnanolone,progesterone,neurosteroid,steroidogenesis,Aldo-keto reductase,c-Src,glioblastoma,glioma,cancer progression
AI Read Science
Must-Reading Tree
Example
![](https://originalfileserver.aminer.cn/sys/aminer/pubs/mrt_preview.jpeg)
Generate MRT to find the research sequence of this paper
Chat Paper
Summary is being generated by the instructions you defined