CRYβB2 alters cell adhesion to promote invasion in a triple-negative breast cancer cell line

African American women with breast cancer experience disproportionately poor survival outcomes, primarily due to the high prevalence of the deadliest subtype; triple-negative breast cancer (TNBC). The CRYβB2 gene is upregulated in tumors from African American patients across all breast cancer subtypes, including TNBC, and is associated with worse survival rates. This study investigated the effect of CRYβB2 on the invasion of TNBC cells and the underlying mechanisms contributing to this phenotype.

We utilized the SUM159 cells with stable CRYβB2 overexpression in a 3D-culture tumor spheroids model in our investigation. A quantitative 3D invasion assay demonstrated that CRYβB2 overexpression significantly enhanced invasion (median invasion %; SUM159 = 0.14 and SUM159 + CRYβB2 = 0.33). RNA sequencing analysis indicated that CRYβB2 overexpression modulated cell-cell adhesion and extracellular matrix organization pathways, which are critical to invasion of cancer cells. Specifically, CRYβB2 suppressed the expression of key cell-cell adhesion genes known as clustered protocadherins and promoted the expression of PCDH7, a nonclustered protocadherin with known oncogenic roles in various cancers. Notably, the knockout of PCDH7 diminished the invasive capacity induced by CRYβB2 (median invasion %; SUM159 = 0.093, SUM159 + CRYβB2 = 0.184 and SUM159 + CRYβB2/PCDH7^-/-=0.082). These findings provide a novel link between a previously identified differentially expressed gene, CRYβB2, in driving breast cancer phenotypes by modulating a class of adhesion proteins.