Journal of Cancer Research
- ISSN: 2578-3726
Zahra Khosravi, Chandrasekaran Kaliaperumal and Arun HS Kumar
Background: Glioblastoma multiform (GBM) is one of the most aggressive and difficult to treat brain tumour in humans with a 5 year survival rate of less than 6%. SERPINE1 is a novel tumour receptor found on GBM that modulates the progression of this cancer through growth signals and remodelling of the extracellular matrix. Hence, we investigated the role of SERPINE1 and its network proteins in pathogenesis of GBM and assessed its target ability.
Material and methods: Network proteins of SERPINE1 in Homo sapiens was identified using the String database, and the affinity of the protein-protein interaction of this network was analysed using Chimera software. The expression profile of SERPINE1 in the different brain regions was evaluated to correlate its relevance to GBM pathology. Selected small molecules from Calotropis gigantea were screened using Auto Dock vina to assess target ability of human SERPINE1.
Results: VTN, PLG, TGFB1, VWF, FGF2 and CXCR1 were identified as the major network proteins of SERPINE1. The strongest interaction was observed between SERPINE1 and FGF2 (42884 H-bonds) followed by CXCR1 (20279 H-bonds). Our results suggest that SERPINE1 and its network proteins identified here play a vital role in GBM development and progression through brain parenchyma by creating the prime microenvironment for carcinogenesis, tumour invasion and migration. The highest expression of SERPINE1 was observed in the pons, medulla, midbrain, corpus callosum and spinal cord. Expression of SERPINE1 was consistent with high grade lesions of GBM, suggesting association of SERPINE1 with advanced stages of GBM. The selected small molecules from Calotropis gigantea were observed to have therapeutically feasible binding affinity (140 - 550 µM) and predicted efficacy (290 - 1115 µM) against human SERPINE1.
Conclusion: SERPINE1 plays a vital role in the progression of GBM through its critical network proteins identified in this study. The expression of SERPINE1 aligns with the advanced stages of GBM. Small molecules from Calotropis gigantea tested in this study can serve as lead compounds for developing novel anti- SERPINE1 therapeutics for advanced stages of GBM.