Novel Thyrointegrin αvβ3 antagonist (fp-PMT) with potent affinity in the treatment of cancer
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ABSTRACT: Microarray analysis was carried out on Glioblastoma (GBM 10181360, GBM 021913 and U87 cells), Bladder cancer (JBV253), skin cancer (A375) and Acute Myelod Leukemia (AML) (KG1A and K562 cells) exposed to fb-PMT at 30 µM concentration. Our genome-wide microarray screens demonstrated that fb-PMT appears to exert its potent anticancer actions on human cancer cells through the molecular interference mechanism with multiple signaling pathways supporting growth and survival of leukemic cells. Notably, fb-PMT had a significant effect on different molecular pathways that contribute to the anticancer activity such as cell cycle control (MYC), survival and maintenance of stem cells (HIF1A; TFAP2C), essential features of the malignant phenotype (TWIST1; SNAI). Furthermore, the fb-PMT-induced significant transcriptional pathway’s activation includes RB1; IRF9; MAML1; RAP1A; and GATA4 pathways, which known to play an important role in anticancer activity. Finally, Consistent with our previous reports on the crosstalk between integrin αvβ3 and ERα which contributes to the induced proliferation of cancer cells, we found that fb-PMT interference with estrogen signaling. The αvβ3 agonist (thyroid hormone) was associated with increased phosphorylation and nuclear enrichment of estrogen receptor α (ERα).
ORGANISM(S): Homo sapiens
PROVIDER: GSE183772 | GEO | 2021/09/11
REPOSITORIES: GEO
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