Growth Factor Independent 1 is a tumor suppressor gene in colorectal cancer
Menée in vitro et à l'aide de xénogreffes de cancer colorectal, cette étude démontre que le gène codant pour le facteur de croissance GFI1 peut exercer une fonction de suppresseur de tumeurs
Colorectal cancer (CRC) is the third most common cancer and the third leading cause of cancer death in the United States. Growth Factor Independent 1 (GFI1) is a zinc finger transcriptional repressor responsible for controlling secretory cell differentiation in the small intestine and colon. GFI1 plays a significant role in the development of human malignancies, including leukemia, lung cancer and prostate cancer. However, the role of GFI1 in CRC progression is largely unknown. Our results demonstrate that RNA and protein expression of GFI1 are reduced in advanced stage non-mucinous CRC. Subcutaneous tumor xenograft models demonstrated that the re-expression of GFI1 in 4 different human CRC cell lines inhibits tumor growth. To further investigate the role of Gfi1 in de novo colorectal tumorigenesis, we developed transgenic mice harboring a deletion of Gfi1 in the distal colon driven by CDX2-cre (Gfi1F/F; CDX2-cre) and crossed them with ApcMin/+ mice (ApcMin/+; Gfi1F/F; CDX2-cre). Loss of Gfi1 significantly increased the total number of colorectal adenomas compared to littermate controls with an APC mutation alone. Furthermore, we found that compound (ApcMin/+; Gfi1F/F; CDX2-cre) mice develop larger adenomas, invasive carcinoma, as well as hyperplastic lesions expressing the neuroendocrine marker chromogranin A, a feature that has not been previously described in APC-mutant tumors in mice. Collectively, these results demonstrate that GFI1 acts as a tumor suppressor gene in colorectal cancer, where deficiency of Gfi1 promotes malignancy in the colon. Implications: These findings reveal that GFI1 functions as a tumor suppressor gene in colorectal tumorigenesis.