Heterogeneity in 2,6-Linked Sialic Acids Potentiates Invasion of Breast Cancer Epithelia

Pally, D and Pramanik, D and Hussain, S and Verma, S and Srinivas, A and Kumar, RV and Everest-Dass, A and Bhat, R (2021) Heterogeneity in 2,6-Linked Sialic Acids Potentiates Invasion of Breast Cancer Epithelia. In: ACS Central Science . (In Press)

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Abstract

Heterogeneity in phenotypes of malignantly transformed cells and aberrant glycan expression on their surface are two prominent hallmarks of cancers that have hitherto not been linked to each other. In this paper, we identify differential levels of a specific glycan linkage: α2,6-linked sialic acids within breast cancer cells in vivo and in culture. Upon sorting out two populations with moderate, and relatively higher, cell surface α2,6-linked sialic acid levels from the triple-negative breast cancer cell line MDA-MB-231, both populations (denoted as medium and high 2,6-Sial cells, respectively) stably retained their levels in early passages. Upon continuous culturing, medium 2,6-Sial cells recapitulated the heterogeneity of the unsorted line whereas high 2,6-Sial cells showed no such tendency. Compared with high 2,6-Sial cells, the medium 2,6-Sial counterparts showed greater adhesion to reconstituted extracellular matrices (ECMs) and invaded faster as single cells. The level of α2,6-linked sialic acids in the two sublines was found to be consistent with the expression of a specific glycosyl transferase, ST6GAL1. Stably knocking down ST6GAL1 in the high 2,6-Sial cells enhanced their invasiveness. When cultured together, medium 2,6-Sial cells differentially migrated to the edge of growing tumoroid-like cocultures, whereas high 2,6-Sial cells formed the central bulk. Multiscale simulations in a Cellular Potts model-based computational environment calibrated to our experimental findings suggest that differential levels of cell-ECM adhesion, likely regulated by α2,6-linked sialic acids, facilitate niches of highly invasive cells to efficiently migrate centrifugally as the invasive front of a malignant breast tumor. ©

Item Type:	Journal Article
Publication:	ACS Central Science
Publisher:	American Chemical Society
Additional Information:	Copyright to this article belongs to American Chemical Society
Keywords:	Activation analysis; Adhesion; Cell culture; Cell membranes; Diseases; Polysaccharides; Potts model, Breast Cancer; Breast cancer cells; Cellular potts models; Computational environments; Extracellular matrices; Glycosyl transferase; Multi-scale simulation; Triple-negative breast cancers, Carboxylic acids
Department/Centre:	Division of Biological Sciences > Molecular Reproduction, Development & Genetics
Date Deposited:	05 Feb 2021 09:42
Last Modified:	05 Feb 2021 09:42
URI:	http://eprints.iisc.ac.in/id/eprint/67871

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