AAA ATPase TRIP13 is overexpressed in prostate cancer and promotes tumor progression

  • Transl Oncol. 2026 Jun:68:102743. doi: 10.1016/j.tranon.2026.102743.
Farrukh Afaq  1 ,  Satya S Pathi  2 ,  Balabhadrapatruni V S K Chakravarthi  1 ,  Darshan Shimoga Chandrashekar  1 ,  Shannon Carskadon  3 ,  Sameer Al Diffalha  1 ,  Lakshmi P Kunju  2 ,  Nallasivam Palanisamy  3 ,  Upender Manne  4 ,  Rajesh Singh  5 ,  Sooryanarayana Varambally  6
Affiliations
  • 1. Department of Pathology, University of Alabama at Birmingham, Birmingham, AL, USA.
  • 2. Department of Pathology, University of Michigan, Ann Arbor, MI, USA.
  • 3. Vattikuti Urology Institute, Department of Urology, Henry Ford Health System, Detroit, MI, USA.
  • 4. Department of Pathology, University of Alabama at Birmingham, Birmingham, AL, USA; O'Neal Comprehensive Cancer Center, University of Alabama at Birmingham, Birmingham, AL, USA. Electronic address: [email protected].
  • 5. Department of Microbiology, Biochemistry and Immunology, Morehouse School of Medicine, Atlanta, GA, USA. Electronic address: [email protected].
  • 6. Department of Pathology, University of Alabama at Birmingham, Birmingham, AL, USA; O'Neal Comprehensive Cancer Center, University of Alabama at Birmingham, Birmingham, AL, USA; Department of Biomedical Informatics and Data Science, University of Alabama at Birmingham, Birmingham, AL, USA. Electronic address: [email protected].
PMID: 42000600 DOI: 10.1016/j.tranon.2026.102743
Abstract

Prostate Cancer (PCa), a common malignancy, is a leading cause of cancer-related deaths among men. Advances in high-throughput technologies have led to the identification of various genetic alterations, including amplifications, deletions, mutations, gene fusions, and aberrant gene expressions, associated with PCa initiation and progression. Identifying key drivers of tumor progression and their underlying signaling pathways contributes to early diagnosis and therapeutic targeting. Here, we showed that thyroid hormone receptor-interacting protein 13 (TRIP13), a member of the AAA-ATPase family is overexpressed in PCa. Additionally, we observed amplification of the TRIP13 locus in a small subset of PCa samples. Functional studies demonstrated that TRIP13 knockdown in PCa cells reduced their proliferation and invasion. Furthermore, ectopic overexpression of TRIP13 in prostate epithelial cells (RWPE-1) resulted in enhanced cell invasion. Additionally, pharmacologic inhibition of TRIP13 by the small molecule inhibitor DCZ0415 suppressed PCa cell proliferation, induced Apoptosis, modulated markers of the epithelial-mesenchymal transition (EMT), and inhibited tumor growth. Overall, these findings highlight a functional role for TRIP13 in PCa progression and demonstrate its potential as a therapeutic target in TRIP13-overexpressing PCa.

Keywords
Apoptosis; Invasion; Metastasis; Prostate Cancer; TRIP13.
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