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

Aims 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. Methods 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. Results 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 . Conclusions 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.