4.5 Review

The emerging roles of ARID1A in tumor suppression

Journal

CANCER BIOLOGY & THERAPY
Volume 15, Issue 6, Pages 655-664

Publisher

TAYLOR & FRANCIS INC
DOI: 10.4161/cbt.28411

Keywords

ARID1A; PI3K; SWI/SNF; chromatin remodeling complex; clear cell carcinoma; endometrial cancer; endometrioid carcinoma; gastric cancer; ovarian cancer; tumor suppressor gene

Categories

Funding

  1. NCI NIH HHS [CA165807, R21 CA165807, R01 CA148826] Funding Source: Medline

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ARID1A has emerged as a tumor suppressor gene, which is mutated in a broad spectrum of cancers, especially in those arising from ectopic or eutopic endometrium. As a subunit of SWI/SNF chromatin remodeler, ARID1A facilitates target-specific binding of SWI/SNF complexes to chromatin, thereby altering the accessibility of chromatin to a variety of nuclear factors. In human cancer, ARID1A possesses not only features of a gatekeeper, regulating cell cycle progression, but also features of a caretaker, preventing genomic instability. An increasing body of evidence suggests crosstalk between ARID1A and PI3K/Akt pathways, and between ARID1A and p53. In this review, we discuss the spectrum of ARID1A alterations in cancers, tumor suppression mechanisms of ARID1A, oncogenic pathways cooperating with ARID1A, and clinical implications of ARID1A mutation.

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