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Sialic Acid Metabolic Engineering of Breast Cancer Cells Interferes with Adhesion and Migration

Manimozhi Nagasundaram1, Rüdiger Horstkorte1, Vinayaga Srinivasan Gnanapragassam1

  • 1Institute for Physiological Chemistry, Medical Faculty, Martin-Luther-University; Halle-Wittenberg, 06120 Halle (Saale), Germany.

Molecules (Basel, Switzerland)
|June 11, 2020
PubMed

Insights

This study engineered breast cancer cells to reduce sialic acids (Sia), a molecule linked to tumor progression and therapy resistance. The findings offer new ways to study and potentially treat breast cancer by altering cell surface sugars.

Area of Science:

  • Biochemistry
  • Glycobiology
  • Cancer Biology

Background:

  • Breast cancer is a leading cause of death in women, characterized by heterogeneity and therapeutic resistance.
  • Protein sialylation, involving sialic acids (Sia), is implicated in tumor progression, metastasis, and resistance to cancer therapies.
  • Understanding breast cancer biology, including sialylation, is crucial for improved diagnosis and treatment strategies.

Purpose of the Study:

  • To investigate the effects of glycoengineering breast cancer cells with non-natural sialic acid precursors.
  • To explore the potential of modulating sialic acid expression for therapeutic strategies in breast cancer.
  • To examine the impact of altered sialic acid levels on cancer cell biology and resistance mechanisms.

Main Methods:

  • MCF-7 breast cancer cells were glycoengineered using non-natural sialic acid precursors with extended acyl side chains.
  • The expression levels of natural sialic acid (N-Acetylneuraminic acid) were quantified after precursor treatment.
  • The expression of polysialic acid (polySia) on NCAM was assessed to evaluate changes in cell adhesion-related glycosylation.

Main Results:

  • Cultivation of MCF-7 cells with non-natural Sia precursors led to a significant reduction in natural N-Acetylneuraminic acid expression.
  • The expression of polySia, a glycosylation affecting cell adhesion, was decreased in the engineered cells.
  • Sialic acid engineering demonstrated a modulation of key glycosylation pathways in breast cancer cells.

Conclusions:

  • Sialic acid engineering provides a novel approach to study the biological functions of Sia in breast cancer.
  • This glycoengineering method offers a valuable toolset for examining complex, Sia-dependent cellular alterations in breast cancer.
  • Modulating sialic acid expression may present new avenues for overcoming therapeutic resistance in breast cancer.
Keywords:
breast cancerglycoengineeringpolysialic acidsialic acidsialic acid precursors

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