Research progress of SWI/SNF complex in breast cancer

Abstract

In the past decade, numerous epigenetic mechanisms have been discovered to be associated with cancer. The mammalian SWI/SNF complex is an ATP-dependent chromatin remodeling complex whose mutations are associated with various malignancies including breast cancer. As the SWI/SNF complex has become one of the most commonly mutated complexes in cancer, targeting epigenetic mutations acquired during breast cancer progress is a potential means of improving clinical efficacy in treatment strategies. This article reviews the composition of the SWI/SNF complex, its main roles and research progress in breast cancer, and links these findings to the latest discoveries in cancer epigenomics to discuss the potential mechanisms and therapeutic potential of SWI/SNF in breast cancer.

Keywords: Breast cancer; Chromatin remodeling; Epigenetics; SWI/SNF.

Fig. 1

The three forms of SWI/SNF complex and subunits of composition: The SWI/SNF complex is composed of products of a total of 29 genes, forming three final forms of complexes containing different variations: BAF, PBAF and ncBAF, each complex is composed of ATPase subunit(yellow), shared subunits(blue and grey) and particular subunits(green)

Fig. 2

Influences ofARID1A and ARID1B on breast cancer: As is illustrated in this figure, ARID1A can affect breast cancer by (a) inhibiting cell migration, (b) mediating endocrine therapy resistance and it has association with metastatic breast cancer. Its expression tend to impact the function of PARP, PIK3CA, PTEN, P53(+) percentage, Ki-67 expression and so on. For ARID1B, its roles include identifying driver mutations, inhibiting cell cycle activity, promoting proliferation, e.t.c. The level of ARID1B expression is associated with the disease-free survival, tumor size and grade, as well as the nuclear polymorphism

Fig. 3

Different mechanisms of BRG1 promoting breast cancer cell proliferation: This figure lists some of the mechanisms that BRG1 promote breast cancer cell proliferation, BRG1 can: (1) operate with E2F transcription factors at gene promoters in proliferation in breast cancer cells, (2) controlling gene transcription, (3) stimulate transcriptional activity of the P53 protein and subsequently inhibiting the activity of tumor suppressor, (4) interact with BRCA1 to remodel chromatin and control the activity of p53 protein