Fig. 7: Schematic summary of the findings. | Cell Death & Differentiation

Fig. 7: Schematic summary of the findings.

From: Targeting TACC3 represents a novel vulnerability in highly aggressive breast cancers with centrosome amplification

Fig. 7

A In cancer cells with CA that can be induced upon PLK4 overexpression, p53 modulation or cytokinesis failure, TACC3 is overexpressed and mediates distinct mitosis and interphase-specific functions to promote cell cycle and tumor progression. Mitotic TACC3 interacts with KIFC1 at the centrosomes and promotes CC to ensure mitotic progression and inhibition of apoptosis. FOXM1 mediates the transcription of TACC3 and KIFC1 during mitosis in p53−/− or mutant cells. Interphase TACC3 interacts with MBD2 and HDAC2, belonging to the NuRD complex, to suppress the transcription of tumor suppressors (i.e., p16, p21, APAF1, KLK10 and DAPK1) and ensures G1/S transition. B Upon TACC3 targeting by a TACC3 inhibitor, BO-264 or si/sh/sgRNAs in cancer cells with CA, while loss of TACC3/KIFC1 interaction at the centrosomes of mitotic cells leads to centrosome de-clustering and mitotic cell death, loss of TACC3/HDAC2/MBD2 interaction at the nucleus of G1 cells leads to transcriptional activation of tumor suppressors to cause G1 arrest and apoptosis that overall culminates in inhibition of tumor growth.

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