Most cancer deaths are due to metastatic dissemination to distant organs. Bone is the most frequently affected organ in metastatic prostate cancer and a major cause of prostate cancer deaths. Yet, our partial understanding of the molecular factors that drive bone metastasis has been a limiting factor for developing preventative and therapeutic strategies to improve patient survival and well-being. Although recent studies have uncovered molecular alterations that occur in prostate cancer metastasis, their functional relevance for bone metastasis is not well understood. Using genome-wide CRISPR activation and inhibition screens we have identified multiple drivers and suppressors of prostate cancer metastasis. Through functional validation, including an innovative organ-on-a-chip invasion platform for studying bone tropism, our study identifies the transcriptional modulator CITED2 as a novel driver of prostate cancer bone metastasis and uncovers multiple new potential molecular targets for bone metastatic disease.
Oncogene. 2024 Mar 07 [Epub]
Juan M Arriaga, Kacey Ronaldson-Bouchard, Florencia Picech, Francisca Nunes de Almeida, Stephanie Afari, Houssein Chhouri, Gordana Vunjak-Novakovic, Cory Abate-Shen
Department of Molecular Pharmacology and Therapeutics, Vagelos College of Physicians and Surgeons, Columbia University Irving Medical Center, New York, NY, 10032, USA. ., Department of Biomedical Engineering, Columbia University, New York, NY, 10032, USA., Department of Molecular Pharmacology and Therapeutics, Vagelos College of Physicians and Surgeons, Columbia University Irving Medical Center, New York, NY, 10032, USA., Department of Oncological Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA., Departments of Molecular Pharmacology and Therapeutics, Urology, Medicine, Pathology & Cell Biology, and Systems Biology, Herbert Irving Comprehensive Cancer Center, Vagelos College of Physicians and Surgeons, Columbia University Irving Medical Center, New York, NY, 10032, USA. .