Table 3.
Functional studies of subunits of the SWI/SNF complexes in PDAC (or other cancers).
| SWI/SNF Subfamily | |
|---|---|
| Subunit | Protein Name/Functional Studies |
| ARID1A (BAF250A) | AT-Rich Interaction Domain 1A. Most mutated subunit in pancreatic cancer. Tumor suppressor. See Section 4.1.1. |
| ARID1B (BAF250B) | AT-Rich Interaction Domain 1B. Tumor suppressor. See Section 4.1.2. |
| PBRM1 (BAF180) * | Polybromo 1. Tumor suppressor. High incidence of truncating mutations [108] and association between PBRM1 loss and tumor response to immunotherapy in clear cell renal carcinoma [109]. PBRM1-deficient renal carcinoma tumors have a distinct transcriptional signature linked to hypoxia and other altered signaling pathways [109,110]. PBRM1 has been shown to regulate stress response in normal epithelial cells and its deletion led to increased proliferation and EMT [111]. |
| SMARCA2 (BRM, BAF190B) | SWI/SNF Related, Matrix Associated, Actin Dependent Regulator of Chromatin, Subfamily A, Member 2. Tumor-suppressive role. See Section 4.1.3. |
| SMARCA4 (BRG1, BAF190A) | SWI/SNF Related, Matrix Associated, Actin Dependent Regulator of Chromatin, Subfamily A, Member 4. Tumor-suppressor and oncogenic roles depending on stage of tumor progression. See Section 4.1.4. |
| SMARCB1 (BAF47, INI1, hSNF5) * | SWI/SNF Related, Matrix Associated, Actin Dependent Regulator of Chromatin, Subfamily B, Member 1. Tumor suppressor linked to pathways associated with tumor proliferation and progression [112]. |
| SMARCC1 (BAF155) | SWI/SNF Related, Matrix Associated, Actin-Dependent Regulator of Chromatin Subfamily C Member 1. See Section 4.1.5. |
| SMARCC2 (BAF170) * | SWI/SNF Related, Matrix Associated, Actin-Dependent Regulator of Chromatin Subfamily C Member 2. Frameshift mutations in SMARCC2 in gastric and colorectal cancers with microsatellite instability [113]. |
| ACTB | Actin Beta. See Section 4.5.1. |
| ACTL6A (BAF53A) | Actin Like 6A. See Section 4.5.2. |
| ACTL6B (BAF53B) * | Actin Like 6B. Aberrant promoter methylation observed in esophageal cancer, liver cancer, and prostate cancer [114,115,116]. See Section 4.1.6. |
| SMARCD1 (BAF60A) * | SWI/SNF Related, Matrix Associated, Actin-Dependent Regulator of Chromatin, Subfamily D, Member 1. Interacts with p53 and mostly acts as a tumor suppressor [117,118]. Decreased expression in ovarian cancer [119] and in lung cancer [117]. SMARCD1 sensitized lung cancer cells to cisplatin-induced apoptosis [117], and its reduced expression triggered cellular senescence in hepatocytes [120]. Opposite results in gastric cancer: overexpressed in gastric cancer tissues and correlated with worse survival outcomes [121]. |
| SMARCD2 (BAF60B) * | SWI/SNF Related, Matrix Associated, Actin Dependent Regulator of Chromatin, Subfamily D, Member 2. Highly expressed in pancreas [122], potential tumor suppressor in leukemia [123]. Involved in chromatin opening of hepatic genes and lineage conversion [124]. |
| SMARCD3 (BAF60C) * | SWI/SNF Related, Matrix Associated, Actin Dependent Regulator of Chromatin, Subfamily D, Member 3. Induced Wnt5a signaling and controlled EMT in breast cancer [125]. Amplified in PDAC (Table 1). |
| SMARCE1 (BAF57) * | SWI/SNF Related, Matrix Associated, Actin Dependent Regulator of Chromatin, Subfamily E, Member 1. Promoted invasive and metastatic progression of breast cancer through upregulation of proteases that degrade ECM by forming a SWI/SNF-independent complex [126]. High expression in metastatic prostate cancer [127]. SMARCE1 loss induced EGFR expression, activated AKT and ERK signaling in lung cancer and conferred resistance to MET and ALK inhibitors [128]. Knockdown led to decreased cell growth and increased sensitivity to anticancer agents in ovarian cancer and breast cancer cell lines [129]. |
| PHF10 (BAF45A) * | PHD Finger Protein 10. Might be neuron specific [56], required for cell proliferation in normal fibroblasts [130]. Tumor suppressor role in uveal melanoma [131]. |
| DPF1/3/2 BAF45B/C/D) * | Double PHD Fingers 1/3/2. Rarely mutated in cancers [132]. |
| ARID2 (BAF200) * | AT-Rich Interaction Domain 2. Tumor suppressor in hepatocellular carcinoma [133,134]. |
| BRD7 * | Bromodomain-Containing Protein 7. Tumor suppressor involved in tumor development and progression in multiple cancers [135]. |
| BRD9, BICRA (GLTSCR1), BICRAL (GLTSCR1L) * | Bromodomain Containing 9/ BRD4 Interacting Chromatin Remodeling Complex Associated Protein/ BRD4 Interacting Chromatin Remodeling Complex Associated Protein Like. Components of a newly identified noncanonical SWI/SNF complex involved in maintaining pluripotency in mouse embryonic stem cells [136]. Amplified in several cancers and may act as oncogenic drivers [137,138]. |
| BCL7 (A/B/C) * | BAF Chromatin Remodeling Complex Subunit BCL7A/B/C. Accumulated in the cell protrusions of migrating pancreatic cells, involved in motility and invasiveness through CREB signaling pathway [91]. Tumor suppressor negatively regulating the Wnt-signaling pathway in gastric cancer cells [139]. |
| BCL11 (A/B) * | BAF Chromatin Remodeling Complex Subunit BCL11A/B. BCL11A: Highly expressed in breast cancer and lung cancer, involved in cancer stemness and tumorigenesis [140,141,142]. BCL11B: overexpression led to chemoresistance in T-cell lines [143], acted as a tumor suppressor in T-cell acute lymphoblastic leukemia [144]. Downregulation in intestinal crypt cells increased expression of β-catenin genes, promoting tumor development [145]. |
| SS18/SS18L1 (CREST) * | SS18 Subunit of BAF Chromatin Remodeling Complex/ SS18L1 Subunit of BAF Chromatin Remodeling Complex. Involved in neural development, and links Ca2+ signaling and chromatin reorganization [146]. |
Note: * No/limited mechanistic studies in PDAC.