Probing Aberrantly Glycosylated Mucin 1 in Breast Cancer Extracellular Vesicles.
Saroj SarojDebashish PaulAkbar AliChrysafis AndreouSuchetan PalTatini RakshitPublished in: ACS applied bio materials (2023)
Aberrantly glycosylated mucin 1 is a critical prognostic biomarker in breast epithelial cancers. Hypoglycosylated mucin 1 coats the surface of the cancer cells, where O -glycans are predominantly linked via an N -acetylgalactosamine moiety (GalNAc). Cancer cell-derived extracellular vesicles (EVs) carry biomarkers from parent cancer cells to the recipient cells and, therefore, could potentially be leveraged for diagnostics and noninvasive disease monitoring. We devised a label-free approach for identifying glycoprotein mucin 1 overexpression on breast cancer EVs. While exploring a plethora of biochemical (enzyme-linked immunosorbent assay, flow cytometry, and SDS-PAGE) and label-free biophysical techniques (circular dichroism and infrared spectroscopy (IR)) along with multivariate analysis, we discovered that mucin 1 is significantly overexpressed in breast cancer EVs and aberrant glycosylation in mucin 1 could be critically addressed using IR and multivariate analysis targeting the GalNAc sugar. This approach emerges as a convenient and comprehensive method of distinguishing cancer EVs from normal samples and holds potential for nonintrusive breast cancer liquid biopsy screening.
Keyphrases
- label free
- papillary thyroid
- childhood cancer
- induced apoptosis
- squamous cell
- cell proliferation
- young adults
- transcription factor
- data analysis
- risk assessment
- cancer therapy
- high throughput
- drug delivery
- lymph node metastasis
- signaling pathway
- endoplasmic reticulum stress
- cell death
- cell cycle arrest
- climate change
- single cell