Sialyl Lewis^X/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 (sLe^X/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 sLe^X/A. Patients with high expression of sLe^X/A had 3 years less disease-free survival than patients with lower expression. In tissue, sLe^X/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 sLe^X/A remarkably increased expression of CK5/6, followed by a decreased proliferation and invasion capacity. Among the reported glycoproteins bearing sLe^X/A and based on the STRING tool, α6 integrin showed the highest interaction score with CK5/6. This is the first report on the sLe^X/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, sLe^X/A is critical for TNBC malignancy and a potential prognosis biomarker and therapeutic target.