In this issue of Cancer Cell, Ogiwara et al. describe a novel link between the epigenetic regulator ARID1A and glutathione metabolism in cancer that is mediated by regulation of the cystine/glutamate transporter XCT.
This study demonstrates that ARID1A-deficient cancer cells are specifically vulnerable to inhibition of the antioxidant glutathione (GSH) and the glutamate-cysteine ligase synthetase catalytic subunit (GCLC), a rate-limiting enzyme for GSH synthesis.
AT-rich interactive domain-containing protein 1A (ARID1A), a SWI/SNF (switch/sucrose nonfermentable) chromatin remodeling gene has context-dependent tumor-suppressive and oncogenic roles in cancer.
AT-rich interaction domain 1A gene (ARID1A) encodes for a subunit of the switch/sucrose non-fermentable (SWI/SNF) complex, a chromatin remodeling complex, and it has been implicated in the pathogenesis of various cancer types.
Mutations in ARID1A that lead to inactivation or loss of expression are frequent and widespread across many cancer types including colorectal cancer (CRC).
Hierarchical and multivariate clustering from both SC+ and tissue cohorts together identified 4 out of 30 endometrioma samples with aberrant expression of stem cell and cancer-associated genes, such as KIT, HIF2α and E-cadherin, altered expression ratio of ER-β/ER-α and downregulation of tumour suppressor genes (PTEN and ARID1A).
We focus on synthetic lethal strategies with ARID1A loss in ovarian clear cell carcinoma, a cancer with the highest ARID1A mutation incidence (46-57%).
Together, these results suggest ARID1A deficiency contributes to impaired MMR and mutator phenotype in cancer, and may cooperate with immune checkpoint blockade therapy.
AT-rich interactive domain-containing protein 1A (ARID1A) and SWItch/sucrose non-fermentable-related, matrix-associated, actin-dependent regulator of chromatin, subfamily a, member 4 are remodeling factors that are mutated in numerous types of cancer.
Higher miR-144-3p may enhance malignancy and resistance to Sunitinib in ccRCC by targeting ARID1A, the observations may uncover novel strategies of ccRCC treatment.