FICAN science -webinaari ”De novo cholesterol biosynthesis as a metabolic vulnerability in rhabdomyosarcoma – implications for novel treatment options”
Julkaistu 11.12.2025
Tervetuloa seuraavaan FICAN webinaariin keskiviikkona 11.2. klo 15. Kansallisten ja kaikille avoimien webinaarien tavoitteena on tarjota ajankohtaista tietoa korkealaatuisesta syöpätutkimuksesta ja sen tuloksista sekä uusimmista kehityksistä ja parhaista käytännöistä eri puolilta Suomea.
11.02 @ 15:00 – 16:00
Puhuja: Professori Riikka Kivelä, Jyväskylän yliopisto
Tutustu puhujaan: Riikka Kivelä | Jyväskylän yliopisto
Aihe: De novo cholesterol biosynthesis as a metabolic vulnerability in rhabdomyosarcoma – implications for novel treatment options
Tällä kertaa seminaarin järjestää FICAN East. Seminaari pidetään verkossa (Microsoft Teams), johon voit liittyä suoraan tästä linkistä: Liity kokoukseen nyt
Abstract
Rhabdomyosarcoma (RMS) is an aggressive pediatric soft-tissue cancer. Identification of RMS precursor cells and models has been a challenge due to unknown molecular mechanisms that drive the common proliferative myogenic phenotype. Our studies have revealed that the PROX1 transcription factor is essential for the growth and myogenic features of RMS, and its downregulation reverts RD cells to a phenotype resembling benign mesenchymal stem cells. Our findings demonstrate that the effects of PROX1 on RMS cell growth are mediated by FGFR, predominantly by FGFR1 and FGFR4, which were found to compensate for each other. Our findings place PROX1 as a major mediator of RMS characteristics and development and suggests that pan-FGFR inhibitors provide a promising option for the treatment of RMS. We have also identified de novo cholesterol biosynthesis as a key metabolic vulnerability in rhabdomyosarcoma, regulated by PROX1. Cholesterol synthesis inhibition halts RMS cell proliferation and triggers ER stress-induced apoptosis, offering a promising therapeutic strategy. The findings highlight a potential therapeutic strategy for rhabdomyosarcoma by targeting de novo cholesterol biosynthesis, as statins are already widely used and well tolerated.
Relevat references from the speaker for this talk:
Gizaw NY, Kallio P, Punger T, Gucciardo E, Haglund C, Böhling T, Lehti K, Sampo M, Alitalo K, Kivelä R. PROX1 transcription factor controls rhabdomyosarcoma growth, stemness, myogenic properties and therapeutic targets. Proc Natl Acad Sci U S A. 2022 Dec 6;119(49):e2116220119. doi: 10.1073/pnas.2116220119.
Gizaw NY, Kolari K, Kallio P, Alitalo K, Kivelä R. Inhibiting cholesterol synthesis halts rhabdomyosarcoma growth via ER stress and cell cycle arrest. EMBO Mol Med. 2025 Dec;17(12):3586-3606. doi: 10.1038/s44321-025-00336-x.
