Conference 2021 Live Talk
F-box only protein FBXO31 functions as a tumor suppressor by inactivating oncogenes associated with ovarian cancer malignancy
Authors and Affiliations
Sehbanul Islam1 and Manas K Santra2
1. PhD student at NCCS, Pune, India
2. Scientist ‘E’ at NCCS, Pune, India
FBXO31, a member of F-box protein family, has been shown to play an important role in DNA damage response and tumorigenesis. It functions as tumor suppressor in most of the cancer or as oncogene in lung cancer. In breast cancer and melanoma, it has been shown that FBXO31 arrest the cells at G1 phase of the cell cycle. However, the role of FBXO31 in ovarian cancer is not known. Previous study showed that FBXO31 (encoded in human chromosome 16q24.3) is inactivated in ovarian cancer due to loss of heterozygosity. Further, TCGA analysis revealed that FBXO31 mRNA levels are low in ovarian cancer. In addition, low FBXO31 level is associated with decreased overall survival of the ovarian cancer patients. We therefore hypothesized that it functions as tumor suppressor in ovarian cancer.
We performed flow cytometry, cell count, colony formation, soft-agar assay, beta-galactosidase staining, western blot etc.
We found that FBXO31 is expressed at very low level in ovarian cancer cell lines and overexpression of FBXO31 inhibits the growth of multiple ovarian cancer cell lines. It arrests the cells at G1 phase of cell cycle and induces senescence. We found that FBXO31 degrades cyclin D1, MDM2 and other oncogenes associated with ovarian cancer malignancy via SCF complex through proteasome mediated pathway. FBXO31 has no effect on CDKs level but stabilizes p21 in a p53 independent manner. Moreover, FBXO31 overexpression inhibited the migration of ovarian cancer cells.
In conclusion, FBXO31 acts as a tumor suppressor by inhibiting growth and migration of ovarian cancer cells by degrading cyclin D1 and MDM2.