Molecular Pathways: SWI/SNF (BAF) Complexes are Frequently Mutated in Cancer-Mechanisms and Potential Therapeutic Insights

“SWI/SNF chromatin remodeling complexes are pleomorphic multi-subunit cellular machines that utilize the energy of ATP hydrolysis to modulate chromatin structure. The complexes interact with transcription factors at promoters and enhancers to modulate gene expression and contribute to lineage specification, differentiation and development. Initial clues to a role in tumor suppression for SWI/SNF complexes came over a decade ago when the gene encoding the SMARCB1/SNF5 core subunit was found specifically inactivated in nearly all pediatric rhabdoid tumors. In the last 3 years, cancer genome sequencing efforts have revealed an unexpectedly high mutation rate of SWI/SNF subunit genes, which are collectively mutated in 20% of all human cancers and approach the frequency of p53 mutations. Here we provide a background on these newly recognized tumor suppressor complexes, discuss mechanisms implicated in the tumor suppressor activity, and highlight findings that may lead to potential therapeutic targets for SWI/SNF mutant cancers.”


Molecular Pathways: SWI/SNF (BAF) Complexes are Frequently Mutated in Cancer-Mechanisms and Potential Therapeutic Insights

“SWI/SNF chromatin remodeling complexes are pleomorphic multi-subunit cellular machines that utilize the energy of ATP hydrolysis to modulate chromatin structure. The complexes interact with transcription factors at promoters and enhancers to modulate gene expression and contribute to lineage specification, differentiation and development. Initial clues to a role in tumor suppression for SWI/SNF complexes came over a decade ago when the gene encoding the SMARCB1/SNF5 core subunit was found specifically inactivated in nearly all pediatric rhabdoid tumors. In the last 3 years, cancer genome sequencing efforts have revealed an unexpectedly high mutation rate of SWI/SNF subunit genes, which are collectively mutated in 20% of all human cancers and approach the frequency of p53 mutations. Here we provide a background on these newly recognized tumor suppressor complexes, discuss mechanisms implicated in the tumor suppressor activity, and highlight findings that may lead to potential therapeutic targets for SWI/SNF mutant cancers.”


Aberrant BAF57 Signaling Facilitates Pro-metastatic Phenotypes

“BAF57, a component of the SWI/SNF chromatin-remodeling complex conglomerate, modulates androgen receptor (AR) activity to promote prostate cancer (PCa). However, the molecular consequences of tumor-associated BAF57 expression have remained undefined in advanced disease such as castration resistant prostate cancer (CRPC) and/or metastasis…The findings herein, identifying tumor-associated BAF57 perturbation as a means to bypass androgen signaling events that facilitate novel pro-metastatic phenotypes, link BAF57 upregulation to tumor dissemination. These data thereby establish BAF57 as a putative marker of metastatic potential that could be leveraged for therapeutic intervention.”