Event Details

11^th February at 15:00–16:00
Online event
in Teams Join the meeting here (Microsoft Teams)

Welcome to the next FICAN Science Webinar with

Prof. Riikka Kivelä, University of Jyväskylä
Denovo cholesterol biosynthesis as a metabolic vulnerability in rhabdomyosarcoma – implications for novel treatmenr options

The webinar is hosted by FICAN East and chaired by Prof. Arto Mannermaa.

These nationwide FICAN webinars provide a platform to share new scientific findings, highlight recent advances in cancer research, and foster collaboration among cancer researchers and clinicians across Finland.

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.

For more information on the FICAN science webinar series, please contact info@fican.fi