SMAD5 and cancer: The Hypoxia-Induced Factors, HIF1 alpha and HIF2 alpha, can be activated by acidic conditions independently of hypoxia.15,16 In the context of cancers, transcription factors SMAD5 and Sterol Regulatory Element-Binding Protein 2 (SREBP2) have been implicated in cellular responses to intracellular pH in cancer cell lines.17,18 It remains to be determined whether and how pH-sensing mechanisms specifically regulate cellular activities in the context of inflammation.