Preliminary study of cyto-impedance: Molecular profiling of functional impedance in motility-promoting treatment of normal cells.

Cell motility is critical for physiological processes including wound healing. However, high concentrations of motility-promoting agents may suppress cellular migration; this newly observed phenomenon warrants further characterization. EH-P002A, a small molecule that enhances cellular motility in vitro and wound healing in vivo, was used to treat two human cell lines HFF-1 and Beas-2B. Whole genome expression profiling was applied. Elevating the EH-P002A concentration to a level far below a cytotoxic concentration resulted in suppression of the migratory abilities of the cells. During this suppression, the expression of WWC2, SMARCA1, PIAS1, PHF8, SDHAF2, and RP11-676M6.1 (a pseudogene) were down-regulated, and MALAT1, NEAT1, MSH6, RN7SL1, AARS, LCP1, APP, ERLIN2, MIEF1, MEGF8, RPS2, PLK1, ENO1, DOCK8, TNRC18, DCAF7, TPT1, RPL3, CAP1, and PLK4 were upregulated. More importantly, two genes, namely PDPK2 and COMMD2, were consistently up-regulated upon EH-P002A treatment regardless of the suppression; and 11 genes consistently down-regulated upon EH-P002A treatment, including RP11-490H24.5, RNF43, MT-ND5, FTL, MT-CO1, RPS6, MT-ND1, MT-ND4, RNU2-2P, MT-CO3, and STT3A. We introduce the term 'cyto-impedance' to describe the phenomenon in which an increase in motility-promoting agent concentration might suppress the drug's effect without detectable cytotoxicity. The gene expression signatures of cyto-impedance have also been preliminary revealed.