Cytoskeletal fractionation identifies LMO7 as a positive regulator of fibroblast polarization and directed migration.

Cell migration is a cytoskeleton-driven cellular process involved in physiological and pathological events such as embryonic development and cancer metastasis. Fibroblasts have often been used to elucidate the mechanism of cell migration due to their high morphological polarity and migratory activity. We recently reported that human lung fibroblasts migrate straight for a long duration without external stimuli, which phenomenon we named intrinsic and directed migration (IDM) of fibroblasts. In this study, we explored proteins involved in IDM in order to elucidate the molecular mechanism. First, we focused on the differences in morphology and migratory behaviors between normal and immortalized fibroblasts-the former exhibit obvious polarity and IDM; the latter exhibit poorly polarized morphology and random migration. We compared the abundance of proteins functioning as the cytoskeletal components between them through proteomic analysis and found that LIM domain only protein 7 (LMO7) is overwhelmingly incorporated into the cytoskeletons of normal fibroblasts. Depletion of LMO7 inhibited the directed migration of normal fibroblast on the fibronectin (FN)-rich surface, suggesting that LMO7 is important for IDM. Moreover, on the FN-free surface, LMO7-depleted fibroblasts often failed to establish morphological polarity and hardly migrated. Thus, the present study identified LMO7 as a positive regulator of fibroblast polarization and IDM, especially in an environment where integrin-mediated substrate attachment is insufficient.