GDF15 and neoplasm: P16INK4A exerts its tumor-suppressing functions for example by terminal cell differentiation following DNA damage.47 Furthermore, low p16INK4A expression level is a predictor of poor treatment response in ovarian cancer patients.48 Thus, the altered tumor histology from an undifferentiated toward a structured, peri-vascular A2780cis tumor together with the enhanced p16INK4A levels in GDF15-knockdown tumors suggests that GDF15 might represent a key factor in the suppression of epithelial cell differentiation, thereby allowing a constitutive self-renewable, stem-like tumor phenotype.