Abstract:
A very well-known hallmark of cancer is chromosomal Instability (CIN). CIN leads to mitotic aberrations and thereby causes chromosome number variations in cancer cells. My study reveals such chromosome modal number changes based on microsatellite and CIN status of the cell line. SW480 microsatellite stable (MSS), CIN+, aneuploid cell line show trends of chromosomal loss on induction of EMT by TWIST1 overexpression. Whereas no such trends were seen in microsatellite instable (MSI), CIN-, hypodiploid HCT116 cell line. Chromosome number changes will affect the gene copy number and thereby the expression levels. In my study c-MYC gene has been seen to undergo copy number variation in SW480 cells on induction of TWIST1. SW480 being an aneuploid cell line should harbour multiple CNVs. Therefore, my study looks towards certain genes like GLCC1 (LncRNA) that stabilize c-MYC expression, Sox2 which is well-known transcription factor help maintain cancer stem cells, and FN1 involved in cancer cell migration and invasion show high heterogeneity. Taken together my study reveals chromosomal instability in cancer cells leads to gene CNV and overexpression of TWIST1 inducing EMT in CRC cell lines extends chromosomal aberrations leading to whole chromosomal losses in CIN+ SW480. TWIST1 induces EMT in CRC via the AKT pathway and c-MYC is a downstream gene in the pathway that promotes proliferation and the heterogeneity in c-MYC copy number reduces on TWIST1 overexpression.
