The review summarizes current knowledge on the Hedgehog signaling pathway, its role in normal embryogenesis and/or initiation and progression of neuro-oncological diseases, especially of high-grade gliomas, the most malignant neuroepithelial tumors. The main proteins forming the Hedgehog signaling pathway include Shh, PTCH1, SMO, HHIP, SUFU and GLI1 isoforms. Effects of other signaling pathways on the family of transcription factors GLI and other proteins are described. The review summarizes modern data about the impact of the Hedgehog signaling pathway on proliferation, migration activity and invasiveness, and also on tumor neoangiogenesis and tumor cell chemoresistance. The role of the Hedgehog signaling pathway in origin of cancer stem cells and epithelial-mesenchymal transition is also analyzed. Some prospects for new anticancer drugs acting on components of the Hedgehog signaling pathway inhibitors are demonstrated.
Proanalizirovany sovremennye predstavleniia o mekhanizmakh funktsionirovaniia signal'nogo puti Hedgehog (HH) i ego vliianii na kletochnye protsessy v normal'nom émbriogeneze i pri neĭroonkologicheskikh zabolevaniiakh, osobenno v razvitii gliom vysokoĭ stepeni zlokachestvennosti. Okharakterizovany osnovnye belki, obrazuiushchie dannyĭ signal'nyĭ put'. Privedeny sovremennye dannye o vliianii puti HH na protsessy proliferatsii, migratsionnoĭ aktivnosti i invazivnosti, opukholevogo neoangiogeneza i priobreteniia opukholevymi kletkami khimiorezistentnosti. Otdel'no rassmotrena rol' belkov puti HH v protsesse épitelial'no-mezenkhimal'nogo perekhoda i pri vozniknovenii i podderzhanii opukholevykh stvolovykh kletok. Pokazany perspektivy sozdaniia novykh protivoopukholevykh preparatov na osnove ingibitorov signal'nogo puti HH.
Keywords: Hedgehog signaling pathway; Shh protein; glioblastoma multiforme; transcription factor GLI.