Synthetic lethality by targeting Aurora A activity in ARID1A-deficient colorectal cancer cells

UM > Faculty of Health Sciences > DEPARTMENT OF PHARMACEUTICAL SCIENCES

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	Synthetic lethality by targeting Aurora A activity in ARID1A-deficient colorectal cancer cells
	Wu, C.; Yang, E. J.; Lyu, J.; Liu, Y.; Zhang, B.; Tan, K.; Wong, K. H.; Shim, J. S.
	2017-05-17
Source Publication	KSBMB International Conference 2017
Abstract	AT-rich interactive domain 1A (ARID1A) has been identified with high frequency of inactivation mutations in a many cancers. Given that ARID1A functions in chromatin remodeling and the maintenance of genomic integrity, we sought to identify synthetic lethal partners of ARID1A by screening epigenetic drug library. Here, we identified that Aurora A Inhibitor I acts in a synthetic lethal manner in ARID1A-deficient cells. Pharmacological and genetic perturbations of its target gene, AURKA, selectively inhibited the growth of ARID1A-deficient cells. From the mechanistic studies, we found that Aurora A expression was negatively regulated by ARID1A. Inhibition of Aurora A activity in ARID1A-deficient cells led to a significant increase in G2/M arrest, multinucleation and apoptosis. These data suggest that ARID1A and Aurora A play an opposite role in regulating G2/M transition and the complementary overexpression of Aurora A in ARID1A-deficient cells is likely to become a target for synthetic lethality. To our knowledge, this is the first data set to demonstrate a synthetic lethality between ARID1A mutation and Aurora A inhibition. Our data indicate that pharmacological inhibition of Aurora A represents a novel strategy to treat cancer harboring ARID1A loss-of-function mutations.
Keyword	ARID1A tumor suppressor synthetic lethality aurora kinase A
Language	英語English
The Source to Article	PB_Publication
PUB ID	32337
Document Type	Conference paper
Collection	DEPARTMENT OF PHARMACEUTICAL SCIENCES Faculty of Health Sciences
Corresponding Author	Shim, J. S.
Recommended Citation GB/T 7714	Wu, C.,Yang, E. J.,Lyu, J.,et al. Synthetic lethality by targeting Aurora A activity in ARID1A-deficient colorectal cancer cells[C], 2017.
APA	Wu, C.., Yang, E. J.., Lyu, J.., Liu, Y.., Zhang, B.., Tan, K.., Wong, K. H.., & Shim, J. S. (2017). Synthetic lethality by targeting Aurora A activity in ARID1A-deficient colorectal cancer cells. KSBMB International Conference 2017.

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