Prof. Tiziano Tuccinardi
PhD project Title:
New molecular targets for cancer therapy
CRC is a leading cause of cancer-related deaths worldwide. Resistance to targeted therapies is the major limit. New therapeutic opportunities to treat CRC patients are required especially in metastatic tumors. A molecular characterization by The Cancer Genome Atlas could be useful in these tumor subtypes to reveal new candidate genes that can be inhibited. Our research group identified SPATS1 (Spermatogenesis-associated serine-rich 1) as amplified oncogene out of 214 candidates. SPATS1 is involved in spermatogenesis. We identified SPATS1 as amplified oncogene in CRC cell lines. We focused on the characterization of this protein that surprisingly showed the appearance of a second band that has a higher molecular weight than the predicted only in CRC cell lines suggesting that this higher band may be tumor specific. Alkaline phosphatase showed that this higher band could be due to hyperphosphorylation. Western blot and immunohistochemistry showed that SPATS1 is cytoplasmic but interestingly it mapped to nuclei as well in CRC. We also checked the expression of SPATS1 in Hek293T cells that have only the lower band corresponding to the predicted molecular weight of the protein to model the expression variation of the bands. In addition, we investigated that SPATS1 promotes CRC cell proliferation and tumorigenesis in 4 CRC cell lines: HCT116, HT29, DLD1, and LoVo. Our aim is to characterize SPATS1 protein and understand its mechanism of action in CRC in vitro and ex vivo. Finally, we want to design and validate SPATS1 inhibitors in CRC models.