PBRM1-dependent PBAF targeting is required for EMT and metastasis in breast cancer

Alisha Dhiman; Mitchell G Ayers; Guanming Jiao; Jamie L McCuiston; Aparna B Shinde; Saeed Salehin Akhand; Juan Jauregui-Lozano; Marco Hadisurya; Elizabeth G Porter; W Andy Tao; Vikki M Weake; Yucheng Zhang; Sagar M Utturkar; Matthew R Marunde; Michael K Wendt; Emily C Dykhuizen

doi:10.1126/sciadv.aed8038

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PBRM1-dependent PBAF targeting is required for EMT and metastasis in breast cancer

Journal article

Open access

Peer reviewed

PBRM1-dependent PBAF targeting is required for EMT and metastasis in breast cancer

Alisha Dhiman, Mitchell G Ayers, Guanming Jiao, Jamie L McCuiston, Aparna B Shinde, Saeed Salehin Akhand, Juan Jauregui-Lozano, Marco Hadisurya, Elizabeth G Porter, W Andy Tao, …

Science advances, Vol.12(31), eaed8038

07/31/2026

DOI: 10.1126/sciadv.aed8038

PMID: 42525774

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Abstract

SWI/SNF chromatin remodelers are represented by three biochemically distinct subcomplexes, the abundant cBAF and the less abundant PBAF and GBAF. Genetics have identified important roles for PBAF in development and disease; however, relating PBAF-mediated phenotypes to biochemical function in chromatin regulation and gene activation has been challenging. Here, we show that the PBRM1 subunit of PBAF is critical for the completion of TGFβ1-mediated epithelial-mesenchymal transition (EMT) of mammary cells in vitro as well as the metastasis of murine breast cancers in vivo. Using epigenomics to profile different stages of EMT, we find that PBRM1 is necessary for targeting PBAF to inducible promoters marked by H3K14ac. We further find that PBRM1 facilitates DNA accessibility at sites bound by TGFβ1-inducible transcription factors, such as Atf3, for the induction of genes involved in migration, cell survival, and inflammation, providing evidence that PBAF is a vulnerability in late-stage metastatic cancers.

Animals

Breast Neoplasms - genetics

Breast Neoplasms - metabolism

Breast Neoplasms - pathology

Cell Line, Tumor

Cell Movement

Chromosomal Proteins, Non-Histone

DNA-Binding Proteins - genetics

DNA-Binding Proteins - metabolism

Epithelial-Mesenchymal Transition - genetics

Female

Gene Expression Regulation, Neoplastic

Humans

Mice

Neoplasm Metastasis

Nuclear Proteins - genetics

Nuclear Proteins - metabolism

Promoter Regions, Genetic

Transcription Factors - genetics

Transcription Factors - metabolism

Transforming Growth Factor beta1 - metabolism

Details

Title: Subtitle: PBRM1-dependent PBAF targeting is required for EMT and metastasis in breast cancer
Creators: Alisha Dhiman - Purdue University West Lafayette
Mitchell G Ayers - Purdue University West Lafayette
Guanming Jiao - Purdue University West Lafayette
Jamie L McCuiston - EpiCypher (United States)
Aparna B Shinde - Purdue University West Lafayette
Saeed Salehin Akhand - Purdue University West Lafayette
Juan Jauregui-Lozano - Purdue University West Lafayette
Marco Hadisurya - Purdue University West Lafayette
Elizabeth G Porter - Purdue University West Lafayette
W Andy Tao - Purdue University West Lafayette
Vikki M Weake - Purdue University West Lafayette
Yucheng Zhang - Purdue University West Lafayette
Sagar M Utturkar - Purdue University West Lafayette
Matthew R Marunde - EpiCypher (United States)
Michael K Wendt - Purdue University West Lafayette
Emily C Dykhuizen - Purdue University West Lafayette
Resource Type: Journal article
Publication Details: Science advances, Vol.12(31), eaed8038
DOI: 10.1126/sciadv.aed8038
PMID: 42525774
ISSN: 2375-2548
eISSN: 2375-2548
Publisher: AMER ASSOC ADVANCEMENT SCIENCE
Grant note: NIH: U01CA207532, R01CA281216, R01EY033734 V Foundation for Cancer Research: V2014-004, D2016-030 American Cancer Society: RSG-21-012-01-DMC Indiana CTSI: TR001108 Office of the Assistant Secretary of Defense for Health Affairs, through the Peer Reviewed Cancer Research Program: W81XWH-17-1-0267 SIRG graduate fellowship from the Purdue Institute for Cancer Research: V2014-004 IU Simon Cancer Center: P30CA082709 Purdue University Center for Cancer Research: P30CA023168 Walther Cancer Foundation National Institutes of Health (NIH): R44GM117683, R44GM116584
E.C.D. is supported by NIH U01CA207532,V Foundation for Cancer Research (V2014-004 and D2016-030), American Cancer Society (RSG-21-012-01-DMC), and Indiana CTSI (TR001108). This work was supported by the Office of the Assistant Secretary of Defense for Health Affairs, through the Peer Reviewed Cancer Research Program, under award no. W81XWH-17-1-0267 to E.C.D. Opinions, interpretations, conclusions, and recommendations are those of the author and are not necessarily endorsed by the Department of Defense. M.K.W. is supported by NIH R01CA281216. V.M.W. is supported by NIH R01EY033734. G.J. is supported by a SIRG graduate fellowship from the Purdue Institute for Cancer Research. We acknowledge support from the IU Simon Cancer Center (grant P30CA082709), Purdue University Center for Cancer Research (grant P30CA023168), and Walther Cancer Foundation. EpiCypher is supported by the National Institutes of Health (NIH) through grants R44GM117683 and R44GM116584.
Language: English
Date published: 07/31/2026
Academic Unit: Holden Comprehensive Cancer Center; Internal Medicine
Record Identifier: 9985215013802771

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