SPATS1: New Molecular Target in Colorectal Cancer

CRC is a leading cause of cancer-related deaths worldwide. More than a million cases are diagnosed annually and the mortality rate is still about 50% underscoring the need for new therapeutic opportunities. A useful molecular characterization in these tumors by TCGA, analyzed these tumor subtypes to reveal new candidate genes that can be inhibited. Our research group identified SPATS1 as an amplified oncogene out of 214 candidates that could negatively influence cell viability in different CRC cell lines using an RNAi screening system. First, we focused on the characterization of SPATS1 protein that surprisingly showed the appearance of a second band with a higher molecular weight than the predicted one mostly in CRC cell lines, proposing that this higher band may be tumor-specific. In addition, we identified SPATS1 as an amplified oncogene in CRC cell lines. SPATS1 was demonstrated to promote oncogenesis by influencing cell viability rate, colony formation capability and cell migration in four CRC cell lines. SPATS1 was also found to be involved in the Wnt/β-catenin pathway and to interact with p53 to accomplish its role in tumorigenesis. Finally, we found a correlation between SPATS1 and GSK3β and CK1 kinases. We found SPATS1 in the cytoplasm of plasma B cells in tissues from a CRC patient, whereas we showed its nuclear localization in cells resembling CRC stem cells. SPATS1 may serve not only as a cancer biomarker, but also as a therapeutic target in CRC treatment.