Enzyme’s Role in Cancer Cell⁣ Growth, ⁤Cholesterol Synthesis Discovered

Updated June 15, 2025

Singapore—Scientists at Duke-NUS Medical School have pinpointed⁣ the previously unknown role of the enzyme FAXDC2 in cancer cell growth. The study,published in the Journal of Clinical⁣ Investigation,reveals the enzyme’s significant‍ role in cholesterol synthesis⁣ and its impact on cancer progression. Researchers suggest that targeting FAXDC2‍ coudl offer new therapeutic interventions for cancer ⁢treatment.

The research details how suppressing FAXDC2 disrupts normal cholesterol synthesis,altering the fate of cancer cells.This disruption highlights a potential weakness in cancer cells that could be exploited for therapeutic purposes. The team initially explored the wnt ⁤signaling pathway, a key regulator of cell ⁣growth, ⁣and discovered FAXDC2’s central role in controlling⁤ cancer and stem cells.

Assistant Professor Babita Madan, ⁣the study’s first author,⁢ said⁢ the discovery of FAXDC2’s ⁤activity, or its suppression, has profound implications for cellular growth and differentiation, illustrating the complex ⁤relationship between cancer biology and cholesterol synthesis.

The study found that hyperactive Wnt signaling, present in the cancer models, impairs cell differentiation, keeping cancers in a stem cell-like state. These undifferentiated cancer stem cells proliferate rapidly, promoting faster tumor progression and resistance ⁢to anti-cancer therapies. When pancreatic cancer models were treated with ETC-159,a Wnt inhibitor made in Singapore,FAXDC2 increased dramatically. ‍Analyses of colorectal cancer tissue‍ samples confirmed FAXDC2 suppression and a buildup of ‍cholesterol precursors, including lophenol.

Professor David Virshup, director of the CSCB Program and senior author, explained that ‍FAXDC2 helps make cholesterol from lophenol. He added that the amount of FAXDC2 in cells changes the amount of lophenol, which appears to ⁣modulate the activity of the differentiation pathway, helping to keep cancer cells in a stem cell-like state.

“FAXDC2 is a previously unknown enzyme that helps make cholesterol from ⁢the precursor lophenol. Importantly, how much FAXDC2 you have in your ‍cells ⁢changes the amount of lophenol you have,” Professor David Virshup ‍said.

Virshup emphasized ⁣the broader implications, stating that the study provides⁢ a glimpse into the molecular ⁣machinery of cancer cells. He said‍ the role of FAXDC2 in regulating cholesterol synthesis opens new pathways for future therapies, emphasizing the importance of cholesterol biosynthesis ‍intermediates as signaling molecules and potential drugs.

What’s next

The team plans to explore ⁢the therapeutic potential of ‍targeting FAXDC2 in cancer treatment, ‍considering it a possible avenue for developing drugs that could inhibit cancer growth by modulating cholesterol synthesis pathways. They are also interested ⁢in preventative strategies to mitigate cancer risk by maintaining the ⁤balance of cholesterol precursors.