Using CRISPR technology, researchers identified a protein known as acyl–coenzyme A binding protein (ACBP) as a key player in the process of cancer metastasis to bones. Their studies revealed that mice with higher levels of ACBP had a greater likelihood of their lung or breast cancer spreading to their bones. This finding was corroborated by an analysis of human genetic data from lung and breast cancers, which showed that elevated ACBP levels were associated with bone metastasis and poorer survival outcomes for patients.

The research, published in Science Translational Medicine, delved into the mechanisms by which ACBP assists cancer cells. It was found that ACBP helps these cells generate energy through a process called fatty acid oxidation (FAO) and also enables them to evade a type of programmed cell death known as ferroptosis.
Crucially, the research team, from the University of Texas MD Anderson Cancer Center, in collaboration with scientists from Rice University and Shanghai Jiao Tong University, tested compounds designed to interfere with ACBP’s activity. When mice implanted with human cancer cells prone to metastasizing to bone were treated with these compounds – imidazole ketone erastin (IKE) and etomoxir – none of the rodents’ cancer spread to their bones. The scientists noted that etomoxir interferes with FAO, while IKE promotes ferroptosis. They concluded that blocking FAO or inducing ferroptosis inhibited bone metastasis in mouse models, suggesting potential applications for clinical treatment.

The methodology used to identify ACBP involved a CRISPR activation screen. The researchers created a library of guide RNA molecules targeting various genes and linked them to CRISPR-derived protein machinery designed to boost the expression of targeted genes. By inserting this machinery into cancer cells, they could then observe which activated genes promoted metastatic behavior.

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