The USP22 Knockout MDA-MB-231 Cell Line is a CRISPR/Cas9-edited knockout cell line derived from the human MDA-MB-231 triple-negative breast cancer cell line, featuring targeted disruption of the USP22 gene. This loss-of-function model provides a clean genetic background for dissecting USP22-dependent chromatin regulation, gene transcription, and oncogenic signaling, generated through CRISPR/Cas9-mediated gene disruption to eliminate USP22 protein expression.
The parental MDA-MB-231 cell line is an estrogen receptor-negative, progesterone receptor-negative, HER2-negative (triple-negative) breast adenocarcinoma line established from a metastatic pleural effusion. Its highly aggressive, invasive epithelial phenotype makes it a standard system for studying metastatic mechanisms, drug resistance, and tumor progression in the absence of traditional hormone receptors.
USP22 encodes a histone deubiquitinase and core SAGA complex subunit that removes ubiquitin from histones H2A and H2B, modulating chromatin to permit transcription of Wnt/??-catenin and NF-??B target genes. Upstream regulators c-MYC, HIF-1??, and FOXM1 control USP22 expression, while USP22 interacts with SIRT1 and SAGA components GCN5, ADA2B, and TAF5L. It enhances transcription of Cyclin D1 and c-Myc downstream of ??-catenin/TCF/LEF, and sustains NF-??B-driven pro-survival programs. Deubiquitination of histones facilitates ??-catenin stabilization, promoting cell cycle progression and epithelial-mesenchymal transition.
In MDA-MB-231 cells, USP22 knockout impairs Wnt/??-catenin and NF-??B signaling, attenuating proliferation, migration, invasion, and metastatic capacity. This isogenic model enables dissection of deubiquitinase-dependent contributions to triple-negative breast cancer aggressiveness, stem cell maintenance, and chemoresistance, with relevance to prostate and colorectal cancers.
Researchers can employ this cell line in assays such as Western blotting, RT-qPCR, Boyden chamber migration/invasion, MTT proliferation, Annexin V apoptosis, TOP/FOP Wnt reporter, co-immunoprecipitation, and ??-catenin immunofluorescence. It is suited for RNA-seq and drug sensitivity screens to identify USP22-linked therapeutic vulnerabilities. Applications include Wnt and NF-??B pathway studies, deubiquitinase target identification, EMT mechanisms, and cancer stem cell analysis. For detailed product information and support, contact Ascent Research.
