CRISPR Screen Unlocks Cancer Metastasis Mystery

The discovery not only enhances our understanding of the disease's molecular underpinnings but also opens new avenues for targeted therapies, potentially revolutionising treatment paradigms for patients battling advanced prostate cancer.

The study meticulously engineered non-metastatic human prostate cancer cell lines to activate or inhibit gene expression using CRISPRa or CRISPRi technology. Engineered cancer cells were then implanted into the prostates of nude mice, and following the development of tumours and the emergence of metastases, both primary and metastatic tumours were harvested for analysis.

The in vivo CRISPR screen identified CITED2 as a significant promoter of bone metastasis, distinguishing itself among various genes for its substantial impact. Subsequent functional validation experiments, including innovative organ-on-a-chip assays, reinforced CITED2's role in promoting bone invasion, underscoring its potential as a therapeutic target.

Furthermore, the research delved into the transcriptional profiles driven by CITED2, revealing distinct patterns in primary and metastatic cancer, which could inform the development of precision medicine approaches.

This research not only marks a significant step forward in the fight against prostate cancer but also exemplifies the power of genetic screening in unveiling critical disease drivers, heralding a new era in oncological research and treatment.

The study was led by Juan Arriaga and Cory Abate-Shen at Columbia University, New York, and it was published today in Oncogene. You can read it here.