ATAD2 Drives Prostate Cancer Progression to Metastasis
Year: 2025
Type: article
Abstract: Metastasis accounts for the overwhelming majority of cancer deaths. In prostate cancer and many other solid tumors, progression to metastasis is associated with drastically reduced survival outcomes, yet the mechanisms behind this progression remain largely unknown. ATPase family AAA domain containing 2 (ATAD2) is an epigenetic reader of acetylated histones that is overexpressed in multiple cancer types and usually associated with poor patient outcomes. However, the functional role of ATAD2 in cancer progression and metastasis has been relatively understudied. Here, we employ genetically engineered mouse models of prostate cancer bone metastasis, as well as multiple independent human cohorts, to show that ATAD2 is highly enriched in bone metastasis compared with primary tumors and significantly associated with the development of metastasis. We show that ATAD2 expression is associated with MYC pathway activation in patient datasets and that, at least in a subset of tumors, MYC and ATAD2 can regulate each other's expression. Using functional studies on mouse bone metastatic cell lines and innovative organ-on-a-chip bone invasion assays, we establish a functional role for ATAD2 inhibition in reducing prostate cancer metastasis and growth in bone. Implications: Our study highlights ATAD2 as a driver of prostate cancer progression and metastasis and suggests it may constitute a promising novel therapeutic target.
Source: Molecular Cancer Research
Institutions: Icahn School of Medicine at Mount Sinai, University of Bern, Columbia University, University Hospital Schleswig-Holstein, Tisch Cancer Institute, University of California, San Francisco, Veracyte (United States), Mayo Clinic, Columbia College - South Carolina, Columbia University Irving Medical Center, Herbert Irving Comprehensive Cancer Center
Language: English
Subfield: Pulmonary and Respiratory Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: green
Awards: G1133076894, G117097001, G1820872495, G2090625567, G20952977, G2284568648, G2933655179, G3388295084, G3475398701, Identification of therapeutic vulnerabilities in prostate cancer bone metastasis, G3881485945, Big Omics Data Engine 2 Supercomputer, G4642493259, G4856100440, G5285582025, G5965728895, G718981360, G7916711296, COVID and Translational Science supercomputer (CATS), G8064862993, G8082411949, G8578167225, Tissue Engineering Resource Center, Multidisciplinary Training in Gastrointestinal Cancers, Investigating cell-intrinsic and extrinsic interactions in prostate cancer at the single cell level, Cancer Center Support Grant
OpenAlex ID: W4407157615