FATE1: A cancer testis antigen with oncogenic functions - Prognostic biomarker and JAK2/STAT1-driven autophagy regulator in breast cancer

Despite being recognized as a critical oncogenic survival factor across multiple malignancies, the functional role and regulatory architecture of Fetal and Adult Testis Expressed 1 (FATE1) in breast Cancer (BC) remain mechanistically obscure. Through integrated online database analysis and validation study, we demonstrate that FATE1 exhibits significant tumor-specific overexpression in BC, correlating with adverse clinical outcomes (HR [hazard ratio] = 2.017, 95 %CI: 1.052-3.869, P = 0.0165) in a 129-patient BC cohort. Functional characterization revealed FATE1 overexpression potentiates proliferative, migratory, and invasive capacities in MCF-7 cells, concomitant with accelerated autophagic flux evidenced by p62 degradation and enhanced LC3-I/II conversion. Genetic ablation of FATE1 in MDA-MB-231 cells reciprocally attenuated these oncogenic phenotypes. Mechanistically, FATE1 orchestrates JAK2/STAT1 pathway activation through upregulation of both JAK2 and STAT1, with concomitant phosphorylation increases. Pharmacological inhibition with JAK-IN-23 (C23H22Cl2N4O, a specific JAK/STAT Inhibitor) abrogated FATE1-mediated oncogenicity and autophagic activity. This work establishes FATE1 as a novel prognostic biomarker and therapeutic target in BC, delineating its oncogenic role in tumor progression through JAK2/STAT1 pathway-mediated proliferation and Autophagy regulation.

Breast cancer; Cancer testis antigen; Fetal and adult testis expressed 1; Mechanism; Prognosis.