Singapore Scientists Uncover A Crucial Link Between Cholesterol Synthesis And Cancer Progression
ON 02/07/2024 AT 02 : 02 AM
The study details the cascade of molecular events beginning from the suppression of FAXDC2 to the disruption of normal cholesterol synthesis to altered cancer fates, highlighting a potential vulnerability in cancer cells that could be targeted for therapeutic intervention.
The research began with a deep dive into the Wnt signaling pathway, known for its critical role in the regulation of both normal and cancer cell growth. Wnt signaling is a key signaling pathway that regulates growth and development and maintaining brain, skin, hair and intestinal cells. However, hyperactive Wnt signaling—present in the cancer models employed in the study—impairs cell differentiation and keeps the cancers in a stem cell-like state. These undifferentiated cancer stem cells proliferate rapidly and uncontrollably, promoting faster tumor progression, and are resistant to anti-cancer therapies.
Employing cutting-edge genomic technologies to unravel this complex biological process, the scientists’ attention was drawn to the enzyme FAXDC2 when they found it increased dramatically after pancreatic cancer models were treated with a made-in-Singapore Wnt inhibitor, ETC-159. In-depth analyses of colorectal cancer tissue samples corroborated this finding, showing a consistent pattern of FAXDC2 suppression and subsequent buildup of cholesterol precursors, including a building block of cholesterol called lophenol. The lower the FAXDC2 expression, the higher the level of lophenol.
Prof Virshup emphasized the broader implications of these insights, saying, “This study provides a fascinating glimpse into the molecular machinery of cancer cells. The role of FAXDC2 in regulating cholesterol synthesis opens new pathways for future therapies. Understanding these complex mechanisms paves the way for innovative approaches to combat cancer, emphasizing the importance of cholesterol biosynthesis intermediates as important signaling molecules and potential drugs.”
The discovery of FAXDC2’s role in cancer biology marks just the beginning of a longer scientific journey. Further research is necessary to fully understand how the suppression of FAXDC2 and the resulting changes in cholesterol metabolism can be leveraged to develop new cancer therapies. The research team is keen on exploring the therapeutic potential of targeting FAXDC2 in cancer treatment, considering it as a possible avenue for the development of drugs that could inhibit cancer growth by modulating cholesterol synthesis pathways.
Additionally, the findings spur interest in preventative strategies that could mitigate the risk of cancer development by maintaining the balance of cholesterol precursors in the body. Understanding the triggers that lead to the suppression of FAXDC2 in cancer cells could pave the way for novel prevention methodologies, potentially offering new hope in the fight against cancer.