Sialyl LewisX/A and Cytokeratin Crosstalk in Triple Negative Breast Cancer

Triple-negative breast cancer (TNBC) encompasses multiple entities and is generally highly aggressive and metastatic. We aimed to determine the clinical and biological relevance of Sialyl-Lewis X and A (sLeX/A)—a fucosylated glycan involved in metastasis—in TNBC. Here, we studied tissues from 50 TNB...

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Bibliographic Details
Published in:Cancers 2023-01, Vol.15 (3), p.731
Main Authors: Pascoal, Carlota, Carrascal, Mylène A., Barreira, Daniela F., Lourenço, Rita A., Granjo, Pedro, Grosso, Ana R., Borralho, Paula, Braga, Sofia, Videira, Paula A.
Format: Article
Language:English
Subjects:
Antibodies
Biomarkers
Breast cancer
Cancer therapies
Cell adhesion
Cells
Cloning
Cytokeratin
Cytoskeleton
Epidermal growth factor
Flow cytometry
Genomes
Glycoproteins
Laboratories
Ligands
Malignancy
Medical prognosis
Metastases
Metastasis
Patients
Prognosis
Proteins
Sialyl Lewis x antigen
Software
Structural proteins
Therapeutic targets
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Summary:Triple-negative breast cancer (TNBC) encompasses multiple entities and is generally highly aggressive and metastatic. We aimed to determine the clinical and biological relevance of Sialyl-Lewis X and A (sLeX/A)—a fucosylated glycan involved in metastasis—in TNBC. Here, we studied tissues from 50 TNBC patients, transcripts from a TNBC dataset from The Cancer Genome Atlas (TCGA) database, and a primary breast cancer cell line. All 50 TNBC tissue samples analysed expressed sLeX/A. Patients with high expression of sLeX/A had 3 years less disease-free survival than patients with lower expression. In tissue, sLeX/A negatively correlated with cytokeratins 5/6 (CK5/6, which was corroborated by the inverse correlation between fucosyltransferases and CK5/6 genes. Our observations were confirmed in vitro when inhibition of sLeX/A remarkably increased expression of CK5/6, followed by a decreased proliferation and invasion capacity. Among the reported glycoproteins bearing sLeX/A and based on the STRING tool, α6 integrin showed the highest interaction score with CK5/6. This is the first report on the sLeX/A expression in TNBC, highlighting its association with lower disease-free survival and its inverse crosstalk with CK5/6 with α6 integrin as a mediator. All in all, sLeX/A is critical for TNBC malignancy and a potential prognosis biomarker and therapeutic target.
ISSN:2072-6694
2072-6694
DOI:10.3390/cancers15030731