Figure 7.

Speculative model suggesting a novel role for Twist1 overexpression in inducing CIN in colorectal cancer cells during EMTs. Twist1 overexpression in colorectal cancer cell lines (i) induces EMT, (ii) downregulates nuclear envelope proteins Lamin A/C, B1 and B2, associated with nuclear aberrations and CIN, (iii) induces DNA double strand breaks that result in enhanced sub-chromosomal alterations and CIN, potentially via p53 and (iv) downregulates cell cycle regulators Bub1, BubR1, Mad1, Mad2 and Aurora B Kinase leading to mitotic defects that contribute to enhanced CIN. In summary, Twist1 overexpression enhances CIN in the context of EMTs, which further contributes to cellular heterogeneity and cancer progression.