DOI: 10.5061/dryad.xksn02vgq
title: BAF155 Methylation Drives Metastasis By Hijacking Super-enhancers and Subverting Anti-tumor Immunity

description: Subunits of the chromatin remodeler SWI/SNF are the most frequently
 disrupted genes in cancer. However, how post-translational modifications
 (PTM) of SWI/SNF subunits elicit epigenetic dysfunction remains unknown.
 Arginine-methylation of BAF155 by coactivator-associated arginine
 methyltransferase 1 (CARM1) promotes triple negative breast cancer (TNBC)
 metastasis. Herein, we discovered the dual roles of methylated-BAF155
 (me-BAF155) in promoting tumor metastasis: activation of
 super-enhanceraddicted oncogenes by recruiting BRD4, and repression of
 interferon / pathway genes to suppress host immune response.
 Pharmacological inhibition of CARM1 and BAF155 methylation not only
 abrogated the expression of an array of oncogenes, but also boosted host
 immune responses by enhancing the activity and tumor infiltration of
 cytotoxic T cells. Moreover, strong me-BAF155 staining was detected in
 circulating tumor cells from metastatic cancer patients. Despite low
 cytotoxicity, CARM1 inhibitors strongly inhibited TNBC cell migration in
 vitro, and growth and metastasis in vivo. These findings illustrate a
 unique mechanism of arginine methylation of a SWI/SNF subunit that drives
 epigenetic dysregulation, and establishes me-BAF155 as a therapeutic
 target to enhance immunotherapy efficacy.
description: Cell cycle arrest : control, JQ1, TP-064, and JQ1+TP-064 in
 MDA-MB-468 cells. Annexin V staining for measurement of
 apoptosis : control, JQ1, and TP-064 in MDA-MB-468 cells.
 Immune cells infiltration in lung tissue : control, JQ1, EZM2302,
 and JQ1+EZM2302 treatment in 4T1.2 injection model (Balb/c
 mice). Immune cells population in blood : control,
 anti-CD8, EZM2302 and anti-CD8+EZM2302 treatment in 4T1.2 injection model
 (Balb/c mice, 10, 20, 30 days).  
description: <strong>Cell cycle arrest (PI
 staining)</strong> JQ1 or TP-064 treatment for 48
 hrs in MDA-MB-468 cells as 3 replicates (DMSO, JQ1, TP-064, and
 JQ1+TP-064). Raw data is included in
 'MDA-MB-468_JQ1_TP-064_cell_cycle_arrest' folder. 
 <strong>Apoptosis Annexin V/PI
 staining</strong> JQ1 or TP-064 treatment for 48
 hrs in MDA-MB-468 cells as 3 replicates (DMSO, JQ1, and TP-064). Raw data
 is included in 'MDA-MB-468_JQ1_TP-064_apoptosis'
 folder.  <strong>T cell infiltration
 Quantification (lung tissue)</strong> Balb/c mice
 injected with 4T1.2 cells was treated with vesicle (7), JQ1 (8), EZM2302
 (8), and JQ1+EZM2302 (8) for 28 days. Lung tissue from mice injected with
 4T1.2 cells was collected and prepared for flow cytometry with CD45-PE,
 CD3-FITC, CD8a-Pe-Cy7, and CD4-APC staining. Raw data is included in
 '4T1.2_JQ1_EZM2302_lung' folder.
 <strong>Immune cells population in
 blood</strong> For detecting immune cells
 population at each time point (10, 20, 30 days), whole blood was collected
 from alb/c mice injected with 4T1.2 cells which was treated with vesicle,
 anti-CD8, EZM2302, and anti-CD8+EZM2302). RBC was removed from whole cell
 blood and stained with CD45-PE, CD3-FITC, CD8a-Pe-Cy7, and CD4-APC for
 flow cytometry. Raw data is included in '4T1.2 antiCD8 EZM2302
 blood' folder. Sample number is variable {10 day and 20 day : vesicle
 (6), anti-CD8 (7), EZM2302 (6), anti-CD8+EZM2302 (6); 30 day : vesicle
 (6), anti-CD8 (5), EZM2302 (5), anti-CD8+EZM2302 (5)}
 All details about the data collection can be found under
 "BAF155 Methylation Drives Metastasis By Hijacking Super-enhancers
 and Subverting Anti-tumor Immunity" at Nucleic Acids
 Research