Many cell-autonomous activities of metformin have been reported, primarily involving activation of AMPK pathway in breast cancer [42], inhibition of AKT-mTORC1 pathway in myeloma [43], suppression of cell cycle progression in esophageal squamous cell carcinomas [44], regulation of MAPK in lung cancer [45], SP1 transcription factor regulation in pancreatic tumor cells [42] and the unfolded protein response (UPR) in prostate cancer [46]. Here, SP1 is linked to esophageal squamous cell carcinoma.