S100A4 promotes metastasis in several types of cancer, but the involved molecular mechanisms are still incompletely described. The protein is associated with a wide variety of biological functions and it locates to different subcellular compartments, including nuclei, cytoplasm and extracellular space. Nuclear expression of S100A4 has been associated with more advanced disease stage as well as poor outcome in colorectal cancer (CRC). The present study was initiated to investigate the nuclear function of S100A4 and thereby unravel potential biological mechanisms linking nuclear expression to a more aggressive phenotype. CRC cell lines show heterogeneity in nuclear S100A4 expression and preliminary experiments revealed cells in G2/M to have increased nuclear accumulation compared to G1 and S cells, respectively. Synchronization experiments validated nuclear S100A4 expression to be most prominent in the G2/M phase, but manipulating nuclear levels of S100A4 using lentiviral modified cells failed to induce changes in cell cycle distribution and proliferation. Proximity ligation assay did, however, demonstrate proximity between S100A4 and cyclin B1 in vitro, while confocal microscopy showed S100A4 to localize to areas corresponding to centrosomes in mitotic cells prior to chromosome segregation. This might indicate a novel and uncharacterized function of the metastasis-associated protein in CRC cells.
Keywords: Cell cycle; Centrosomes; Colorectal cancer; Cyclin B1; Nucleus; S100A4.