Gene of the Month – January: ARID1A
A recently published study describes that the ARID1A gene plays a role in hormone dependency of tumor cells in breast cancer and provides new insights into the processes that lead to endocrine resistance of breast cancer cells. ARID1A is a subunit of the SWI/SNF complex, which comprises several proteins that change chromatin structure and thereby regulate the accessibility of DNA elements for transcription. Inactivating ARID1A mutations are the most common alterations in SWI/SNF complex genes present in estrogen-receptor-positive (ER+) breast cancer.
The researchers investigated patients with metastatic breast cancer and found that tumor cells with ARID1A alterations responded poorly to endocrine therapy, which suggests reduced hormone dependency of the tumor cells in these women. ER+, or luminal, tumors have receptors that attach to estrogen and depend on the hormone to grow. Endocrine therapy thus aims at blocking the formation or action of estrogen. However, the majority of patients with metastatic breast cancer develop resistance to these hormone therapy agents. The CRISPR/Cas9-based cell experiments performed in the study shed new light on the processes that lead to the change in tumor cells and a reduced sensitivity to luminal-specific endocrine therapy. They suggest that inactivation of ARID1A causes altered chromatin remodeling and thereby promotes the switch of tumor cells from luminal cells to basal-like cells and the development of hormone resistance.
The results of the study were published in Nature Genetics.
Xu G, Chhangawala S, Cocco E, …, Toska E. ARID1A determines luminal identity and therapeutic response in estrogen-receptor-positive breast cancer. Nat Genet. 2020 Jan 13. doi: 10.1038/s41588-019-0554-0. [Epub ahead of print]