Studying Oscillations of SNAIL in Breast Cancer Models of Varying Malignancy Using a SNAIL-Luciferase Reporter
Circadian rhythms are innate biological timekeeping mechanisms that follow a roughly 24-hour rhythmic cycle. Epidemiological evidence demonstrates that circadian rhythm disruption has been associated with an increased susceptibility to a variety of diseases, including cancers. At the molecular level, circadian rhythms are controlled by a transcriptional-translational feedback loop consisting of four core clock proteins that regulate the expression of various clock-controlled genes including cancer-associated markers like SNAIL. SNAIL is a protein implicated in epithelial-to-mesenchymal transition in cells, and is associated with cancer metastasis, as well as invasiveness, resistance to apoptosis, and poor patient prognosis. The presence of E-box regions in SNAIL’s promoter sequence, known to be key binding regions to core clock proteins, indicates that SNAIL is likely under circadian control.
Therefore, I am studying SNAIL expression in relation to cancer in a high resolution, time dependent manner to facilitate understanding of the relationships among SNAIL, circadian rhythms, and tumor aggressiveness. By using a SNAIL:Luciferase reporter construct and stably transfecting the plasmid into target cancer cell lines of varying malignancy, we monitored the bioluminescent oscillations of SNAIL. We hypothesized that SNAIL would oscillate in a circadian manner, and that there would be a connection between altered circadian oscillations and varying levels of cancer aggression. I observed that the standard circadian model U2OS cell line shows robust SNAIL circadian rhythms, however, these are absent in the highly aggressive breast cancer cell line MDA-MB-231. Assessments in other breast cancer cells are pending.
Research Area | Presenter | Title | Keywords |
---|---|---|---|
Genetics | Hoffenberg, Molly Elena | Breast Cancer | |
Cancer Studies | Taig, Gaia | Breast cancer | |
Cancer Studies | Lee, Hannah | Breast cancer | |
Cancer Studies | Zheng, Aspen | epithelial-mesenchymal transition (EMT) |