Early in vitro results indicate that de-O-acetylated sialic acids increase Selectin binding in cancers

Sep 21, 2026

Early in vitro results identify de-O-acetylated sialic acids as functional modifiers of the Sialic Acid–Selectin axis used during cancer metastasis. The study focuses on how deviations from canonical Sia structure regulate binding to Selectin receptors (E, L, and P) on hemopoietic cells. Using CRISPR-Cas9 gene editing to modulate O-acetylation states and sialyl glycan recognition probes to generate O-acetylated or de-O-acetylated Sia, experiments show increased cell-surface expression and higher Selectin binding, proliferation, and migration in lung and colon cancer models. Mechanistic evidence supports glycan functional-group specificity for therapeutic development, including glycan-based therapeutic strategies such as enzyme–antibody drug conjugates.

LanguageEnglish

CategoryResearch & Report

FormatPDF

Pages19

Reading Time48 min

AccessFree to download

Introduction

Cancer metastasis and the Selectin–sialic acid pathway

Non-canonical sialic acid as a Selectin ligand

Rationale for targeting Sia functional-group acetylation states

TYPE Original Research PUBLISHED 09 December 2024 DOI 10.3389/fonc.2024.1443303 OPEN ACCESS EDITED BY Lubor Borsig, University of Zurich, Switzerland REVIEWED BY Roger Chammas, University of São Paulo, Brazil Giselle Hevia Hernandez, University of Bern, Switzerland *CORRESPONDENCE Rachel Willand-Charnley [rachel.willand@sdstate.edu](rachel.willand@sdstate.edu) †These authors have contributed equally to this work RECEIVED 03 June 2024 ACCEPTED 11 November 2024 PUBLISHED 09 December 2024 CITATION Das K, Schulte M, Gerhart M, Bayoumi H, Paulson D, Fink DM, Parrish C and Willand-Charnley R (2024) Early in vitro results indicate that de-O-acetylated sialic acids increase Selectin binding in cancers. Front. Oncol. 14:1443303 . doi: 10.3389/fonc.2024.1443303 COPYRIGHT © 2024 Das, Schulte, Gerhart, Bayoumi, Paulson, Fink, Parrish and Willand-Charnley. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY) . The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. Early in vitro results indicate that de-O-acetylated sialic acids increase Selectin binding in cancers Kakali Das 1†, Megan Schulte 1†, Megan Gerhart 1†, Hala Bayoumi 1, Delayna Paulson 1, Darci M. Fink 1, Colin Parrish 2 and Rachel Willand-Charnley1* 1 Department of Chemistry, Biochemistry and Physics, South Dakota State University, Brookings, SD, United States, 2 Department of Microbiology and Immunology,Baker Institute for Animal Health, College of Veterinary Medicine, Cornell University, Ithaca, NY, United States Cancers utilize a simple glycan, Sialic Acid, to engage in metastatic processes via the Sialic acid (Sia) -Selectin pathway. Selectins recognize and bind to sialylated substrates, resulting in adhesion, migration, and extravasation, however, how deviations from the canonical form of Sia regulate binding to Selectin receptors (E, L, and P) on hemopoietic cells resulting in these metastatic processes, remained a gap in knowledge. De-O-acetylated Sias has been recently shown to be an integral substrate to the binding of sialic acid binding proteins. The two proteins responsible for regulating the acetyl functional group on Sia’s C6 tail, are Sialic acid acetylesterase (SIAE) and Sialic acid O acetyltransferase (CASD1) . To elucidate the contribution of functional group alterations on Sia, 9-O and 7,9-Oacetylation of Sia was modulated via the use of CRISRP-Cas9 gene editing and with Sialyl Glycan Recognition Probes, to produce either O-acetylated-Sia or deO-acetylated-Sia, respectively. In vitro experiments revealed that increased cell surface expression of de-O-acetylated-Sia resulted in an increase in Selectin binding, enhanced cell proliferation, and increased migration capabilities both in lung and colon cancer. These results delineate for the ﬁrst time the mechanistic contribution of de-O-acetylated-Sia to Selectin binding, reinforcing the importance of elucidating functional group alterations on Sia and their contribution. Without accurate identiﬁcation of which functionalized form of Sia is being utilized to bind to sialic acid binding proteins, we cannot accurately produce glycan therapeutics with the correct speciﬁcity and reactivity, thus this work contributes an integral component in the development of promising therapeutic avenues, for example in the realm of enzyme antibody drug conjugates. KEYWORDS de-O-acetylated sialic acid, cancer, selectins, sia-selectin pathway, Sialyl Lewis X, PSGL-1, metastasis, migration Frontiers in Oncology 01 [frontiersin.org](frontiersin.org) Introduction Cancer uses simple sugar residues to engage in metastatic processes (1) via the Sel

FAQs

What question does the study address about sialic acid and Selectins?

The work examines how non-canonical deviations in the Sia structure regulate binding to Selectin receptors (E, L, and P) and thereby contribute to metastatic processes.

How were O-acetylated vs de-O-acetylated sialic acid forms generated for experiments?

CRISPR-Cas9 gene editing was used to modulate 7,9-O and 9-Oacetylation states of Sia, and sialyl glycan recognition probes were used to produce and detect the O-acetylated or de-O-acetylated forms.

What in vitro effects were observed when de-O-acetylated Sia increased on cell surfaces?

In vitro results showed increased Selectin binding, enhanced cell proliferation, and improved migration capabilities in lung and colon cancer.

Sep 21, 2026

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