Therefore, the positive feedback loop between PI3K/AKT and RUNX2 strengthens the collaboration between SMADs and RUNX2 and between PI3K/AKT and TGFβ and participates in the reprogramming of cancer cells to express EMT transcription factors, MMPs, VEGF, bone matrix proteins, bone-resorbing factors, and other products of genes associated with invasion and metastasis. Here, RUNX2 is linked to cancer.