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

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 αB-crystallin ( CRYAB ) is more highly expressed in the basal-like subtypes than in the oth...

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Bibliographic Details
Published in:Scientific reports Vol. 13; no. 1; p. 4010
Main Authors: Yang, Lili, Haga, Yuya, Nishimura, Akihide, Tsujii, Yuki, Tanahashi, Suzuno, Tsujino, Hirofumi, Higashisaka, Kazuma, Tsutsumi, Yasuo
Format: Journal Article
Language:English
Published: London Nature Publishing Group UK 10-03-2023
Nature Publishing Group
Nature Portfolio
Subjects:
5-Fluorouracil
631/67/1347
631/80/84
alpha-Crystallin B Chain - genetics
Breast cancer
Cell adhesion & migration
Cell Line, Tumor
Cell migration
Cell Movement
Chemotherapy
Crystallin
Fluorouracil
Humanities and Social Sciences
Humans
Metastases
Metastasis
Motility
multidisciplinary
Science
Science (multidisciplinary)
siRNA
Survival
Triple Negative Breast Neoplasms - metabolism
Tumor cell lines
Wound healing
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Summary: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 αB-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 αB-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 αB-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 αB-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 αB-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, αB-crystallin expression. These results suggest that 5-FU–induced cell migration is mediated by αB-crystallin in the BL2 subtype of TNBC.
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ISSN:2045-2322
2045-2322
DOI:10.1038/s41598-023-31186-7