We have shown that in addition to its well recognized nuclease activity, MRE11 promotes EMT and cancer stemness through nuclease independent activation of RUNX2, CXCR4, and AKT to inhibit FOXA2/E-cadherin, leading to cancer growth and metastasis, radio- and chemoresistance, and poor survival in oral cancer patients (Fig. 6J). Here, FOXA2 is linked to lip and oral cavity carcinoma.