GDF15 contributes to thyroid cancer progression and modulates thyroid cancer cell senescence in a p53-dependent manner.

Growth differentiation factor 15（GDF15）displays aberrant expression in multiple malignancies, yet its role and underlying mechanisms in thyroid carcinoma remain unclear. This study aimed to investigate GDF15 expression and functional significance in thyroid cancer, revealing that GDF15 is significantly upregulated and participates in cellular senescence. GDF15 knockdown suppresses proliferation, migration, and invasion of thyroid cancer cells. Transcriptome sequencing demonstrates that GDF15 depletion activates the p53 pathway and induces senescence. Furthermore, our results confirm a protein-level interaction between GDF15 and p53. Given the established importance of p53 in senescence, p53 knockdown partially rescues the enhanced senescence phenotype induced by GDF15 depletion. Consequently, we identify a novel GDF15-p53 regulatory loop wherein GDF15 sustains thyroid carcinogenesis by suppressing p53-dependent senescence. Targeting this axis highlights a promising therapeutic target for thyroid carcinoma, with GDF15 inhibition representing a tumor senescence reactivation strategy.