AI Article Synopsis
- The study investigates the role of β1,3-Galactosyltransferase 5 (B3GALT5) in breast cancer, highlighting its association with disease progression and poor clinical outcomes, particularly in early-stage patients.
- Using tissue samples from 202 women, the researchers found that higher levels of B3GALT5 correlated with shorter overall and relapse-free survival rates.
- In vitro and in vivo experiments revealed that B3GALT5 promotes cancer cell behaviors such as migration, invasion, and epithelial-to-mesenchymal transition (EMT), underscoring its potential as a prognostic marker and therapeutic target in breast cancer treatment.
Article Abstract
Background: Existence of breast cancer stem cells (BCSCs) is implicated in disease relapse, metastasis, and resistance of treatment. β1,3-Galactosyltransferase 5 (B3GALT5) has been shown to be a pro-survival marker for BCSCs. However, little is known about the prognostic significance of B3GALT5 in breast cancer.
Methods: Paired tissues (tumor part and adjacent non-tumor part) from a cohort of 202 women with breast cancer were used to determine the expression levels of B3GALT5 mRNA by qRT-PCR. Kaplan-Meier and multivariable Cox proportional hazard models were used to assess survival differences in terms of relapse-free survival (RFS) and overall survival (OS). Both breast cancer cells and cancer stem cells (BCSCs) were used to see the in vitro effects of knockdown or overexpression of B3GALT5 on cell migration, invasion, and epithelial-to-mesenchymal transition (EMT). A patient-derived xenograft (PDX) model was used to see the in vivo effects of knockdown of B3GALT5 in BCSCs on tumor growth and metastasis.
Results: Higher expression of B3GALT5 in 202 breast cancer tissues, especially in adjacent non-tumor tissue, correlated with poor clinical outcomes including shorter OS and RFS in all patients, especially those with early stage breast cancer. In vitro studies showed B3GALT5 could enhance cell migration, invasion, mammosphere formation, and EMT. Of note, B3GALT5 upregulated the expression of β-catenin and EMT activator zinc finger E-box binding homeobox 1 (ZEB1) pathway in BCSCs. In vivo studies showed B3GALT5 expression in BCSCs is critical for not only tumor growth but also lymph node and lung metastasis in PDX mice.
Conclusion: Our results demonstrated the value of B3GALT5 as a prognostic marker of breast cancer, especially among the early stage patients, and its crucial roles in regulating EMT, cell migration, and stemness thereby promoting breast cancer progression.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7792347 | PMC |
| http://dx.doi.org/10.1186/s13058-020-01381-9 | DOI Listing |
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