Fluorouracil exacerbates alpha-crystallin B chain-mediated cell migration in triple-negative breast cancer cell lines

Among triple-negative breast cancer (TNBC) subtypes, the basal-like 2 (BL2) subtype shows the lowest survival rate and the highest risk of metastasis after treatment with chemotherapy. Research has shown that alpha B-crystallin (CRYAB) is more highly expressed in the basal-like subtypes than in the other subtypes and is associated with brain metastasis in TNBC patients. We therefore hypothesized that alpha B-crystallin is associated with increased cell motility in the BL2 subtype after treatment with chemotherapy. Here, we evaluated the effect of fluorouracil (5-FU), a typical chemotherapy for the treatment of TNBC, on cell motility by utilizing a cell line with high alpha B-crystallin expression (HCC1806). A wound healing assay revealed that 5-FU significantly increased cell motility in HCC1806 cells, but not in MDA-MB-231 cells, which have low alpha B-crystallin expression. Also, cell motility was not increased by 5-FU treatment in HCC1806 cells harboring stealth siRNA targeting CRYAB. In addition, the cell motility of MDA-MB-231 cells overexpressing alpha B-crystallin was significantly higher than that of MDA-MB-231 cells harboring a control vector. Thus, 5-FU increased cell motility in cell lines with high, but not low, alpha B-crystallin expression. These results suggest that 5-FU-induced cell migration is mediated by alpha B-crystallin in the BL2 subtype of TNBC.

Automated summary

Among TNBC subtypes, the BL2 subtype has the lowest survival rate and highest risk of metastasis after chemotherapy treatment. Alpha B-crystallin (CRYAB) is highly expressed in BL2 subtypes and is associated with brain metastasis in TNBC patients. We hypothesized that alpha B-crystallin is associated with increased cell motility in the BL2 subtype after chemotherapy.