Wan Sheng Liu | Shared RAR Pathway Mechanisms of PRAME Cancer/Testis Antigens in Germ Cells & Tumors

Wan-Sheng Liu, The Pennsylvania State University, United States Title: Shared RAR Pathway Mechanisms of PRAME Cancer/Testis Antigens in Germ Cells and Tumors Abstract: The PRAME (Preferentially Expressed Antigen in Melanoma) gene family represents a unique class of cancer/testis antigens with a dual biological identity: immune-linked tumor markers and essential regulators of germ cell development. Across malignancies, PRAME is aberrantly reactivated and functions as a potent tumor-associated antigen that promotes immune evasion and uncontrolled proliferation. Mechanistically, PRAME represses retinoic acid (RA)–dependent transcription by binding and inhibiting retinoic acid receptors (RARs), thereby blocking RA-driven differentiation programs that normally constrain cell growth. This RA-antagonistic activity, coupled with its nearly germ-cell-restricted expression in healthy tissues, has elevated PRAME as a promising biomarker and target for cancer immunotherapy. In reproduction, we uncovered a parallel RA-regulatory role using Pramex1 and Pramel1 single- and double-knockout mouse models. Loss of both factors revealed synergistic disruption of RA-responsive transcriptional networks during spermatogonial differentiation and meiotic initiation. The double mutants showed substantially stronger defects than either single knockout, indicating functional redundancy and cooperative control of RA signaling during gametogenesis. These findings position PRAME paralogs not merely as passive cancer biomarkers but as active modulators of a conserved developmental pathway essential for germ cell maturation. By integrating tumor biology with reproductive genetics, our work highlights a shared RAR-dependent molecular mechanism underlying PRAME function across two biologically distant systems. Understanding how PRAME proteins tune RA sensitivity in germ cells and tumors offers a framework for dissecting differentiation checkpoints, predicting tumor RA-response states, and designing context-specific therapeutic strategies. Elucidating this conserved pathway may ultimately enable dual innovations: enhancing cancer immunotherapies targeting PRAME while revealing fundamental principles of RA-regulated germ cell development. #WCCRT2026 #cancerresearch #cancertherapy #oncology #CancerConference #medicalconferences #healthcareinnovation #cancerawareness #immunotherapy #precisionmedicine #cancertreatment #oncologyresearch #globalhealth #medicalscience #cancercare #cancercommunity #cancerbreakthrough #lifesciences #clinicalresearchcoordinator #oncologista #oncologie #cancer #cancertarot #cancerawareness #oncologyresearch #medicaloncology #radiationoncology #surgicaloncology #pediatriconcology #oncologycare #oncologyinnovation #oncologyexperts #cancerbiology #molecularoncology #targetedtherapy #CancerImmunology #oncologynursing #CancerEpidemiology #OncologyAdvances #cancerprevention #earlydetection #cancerscreening #oncologyeducation