Coherently, we observed that silencing of individual enzymes involved in lipid metabolism—specifically FASN, SCD, and HMGCR—is not sufficient to fully replicate the phenotype of RUNX2 KD, while the knockdown of SREBP1, their upstream regulator, successfully phenocopied the RUNX2 silencing in TC cells, strongly impacting on cancer cell aggressive behaviors. Here, SCD is linked to cancer.