Publication Date:
2018
Description:
〈sec〉〈st〉Synopsis〈/st〉〈p〉〈textbox textbox-type="graphic"〉〈p〉〈inline-fig〉〈/inline-fig〉〈/p〉〈/textbox〉〈/p〉
〈p〉Centrosome amplification is frequently observed in human tumors yet cancer cells manage to circumvent cell death by centrosome clustering and generation of a pseudo-bipolar spindle. Here, genetically perturbing interaction between centrosomal-P4.1-associated protein (CPAP) and tubulin in extra-centrosome-containing cancer cells is found to activate centrosomes before the onset of mitosis thereby selectively inducing mitotic catastrophe.〈/p〉
〈p〉 〈l type="unord"〉〈li〉〈p〉The CPAP-tubulin interaction is a cancer cell-specific target.〈/p〉〈/li〉
〈li〉〈p〉The small-molecule compound CCB02 inhibits CPAP-tubulin interaction, binding at the CPAP binding site of β-tubulin.〈/p〉〈/li〉
〈li〉〈p〉Inhibition of CPAP-tubulin interaction is sufficient to enhance pericentriolar material recruitment and activate extra centrosomes.〈/p〉〈/li〉
〈li〉〈p〉Extra-centrosome activation prevents centrosome clustering and reduces proliferation of centrosome amplified cancer cells 〈i〉in vitro〈/i〉 and tumorigenesis 〈i〉in vivo〈/i〉.〈/p〉〈/li〉〈/l〉 〈/p〉〈/sec〉
Print ISSN:
0261-4189
Electronic ISSN:
1460-2075
Topics:
Biology
,
Medicine