AQP3, one of the aquaglyceroporins, might cause EMT via metabolic reprogramming. Go Yoshida, Tokyo Medical and Dental University 29 July 2014 Accumulating evidence suggests that aquaporins (AQPs) play a crucial role not only in the homeostasis of the normal tissue but also in the development and progression of autoimmune disorders and malignant neoplasms. AQP-3, -7, -9 belong to the aquaglyceropolins, which permit the penetration of glycerol as well as water through the lipid cellular membrane. It has been reported that TNF-alpha decreases the expression of AQP-3 through the activation of p38 and extracellular signal-regulated kinase (ERK) signaling pathways (Mol Cell Biol 2008;28:326-332.). However, less is known about which subtype of aquaglyceropolin is highly expressed in cancer cells. In this article, the authors demonstrated, using two kinds of gastric cancer cell lines, that si-RNA-mediated AQP3 depletion induced mesenchymal-epithelial transition (MET) or prevented EMT. Activation of EGFR signal transduction resulted in the up-regulation of AQP-3. Activation of EGFR signal pathway partially rescued AQP3 depletion in terms of EMT in Figure3-4. In Figure5, the authors failed to demonstrate whether or not overexpression of AQP3 was really responsible for EMT in gastric cancer cells. Further, the authors should have evaluated phosphorylated-Akt as well as Akt and other EMT-inducer transcription factors other than Snail in Figure6. As far as I have performed several experiments on AQP3 in cancer tissues, EGFR signal pathway up-regulated AQP3. AQP3, 7, and 9 contribute to the uptake of glycerol, thereby promoting the lipid metabolism. That is why the following two points exist the authors should more investigate; Firstly, the crosstalk between EGFR signal and PI3K/Akt/Snail axis should be focused on. And secondly, they should study whether or not AQP3-induced metabolic reprogramming is related to EMT. Competing interests No Competing Interests Exist.