FOXM1 in sarcoma: role in cell cycle, pluripotency genes and stem cell pathways

摘要: FOXM1 is a pro-proliferative transcription factor that promotes cell cycle progression at the G1-S, and G2-M transitions. It activated by phosphorylation usually mediated successive cyclin - dependent kinase complexes, highly expressed in sarcoma. p53 down regulates inhibition also partly on Rb p21. Abnormalities of or are frequent sporadic sarcomas with bone soft tissue sarcoma, accounting for 36% index cancers high penetrance TP53 germline disorder, Li-Fraumeni syndrome.FOXM1 stimulates pluripotency related genes including SOX2, KLF4, OCT4, NANOG many which important disorder mesenchymal stem cell/ partially committed progenitor cells. In selected specific, SOX2 uniformly synovial Embryonic pathways preferentially used such as Hippo, Hedgehog, Wnt dominate stoichiometry to alter rates production degradation. undifferentiated pleomorphic liposarcoma, fibrosarcoma, dysregulation Hippo pathway increases expression effector co-transcriptional activator Yes-Associated Protein (YAP). A complex involving YAP TEAD elevates these sarcoma subtypes. another scenario 80% desmoid tumors have nuclear localization β-catenin, molecule. Thiazole antibiotics inhibit because they an auto-regulator loop inhibited. Current systemic treatment limited efficacy inhibiting represents potential new strategy.