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Sialyl LewisX/A and Cytokeratin Crosstalk in Triple Negative Breast Cancer
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Orientador(es)
Resumo(s)
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.
Descrição
project LA/P/0140/2020 of the Associate Laboratory Institute for Health and Bioeconomy—i4HB.
Publisher Copyright:
© 2023 by the authors.
Palavras-chave
aberrant glycosylation cytokeratin expression disease-free survival rate intermediate filament proteins sialyl Lewis (sLe) triple-negative breast cancer (TNBC) α6 integrin Oncology Cancer Research SDG 3 - Good Health and Well-being