Integrating transcriptomics, proteomics, glycomics and glycoproteomics to characterize paclitaxel resistance in breast cancer cells

Lin Cao; Yue Zhou; Xiang Li; Shuai Lin; Zengqi Tan; Feng Guan

doi:10.1016/j.jprot.2021.104266

Integrating transcriptomics, proteomics, glycomics and glycoproteomics to characterize paclitaxel resistance in breast cancer cells

J Proteomics. 2021 Jul 15:243:104266. doi: 10.1016/j.jprot.2021.104266. Epub 2021 May 14.

Authors

Lin Cao¹, Yue Zhou², Xiang Li³, Shuai Lin⁴, Zengqi Tan¹, Feng Guan⁵

Affiliations

¹ International Research Laboratory of Glycobiology and Medicinal Chemistry, College of Life Science, Northwest University, Xi'an 710069, PR China.
² International Research Laboratory of Glycobiology and Medicinal Chemistry, College of Life Science, Northwest University, Xi'an 710069, PR China; The Key Laboratory of Carbohydrate Chemistry & Biotechnology, Ministry of Education, School of Biotechnology, Jiangnan University, Wuxi, China.
³ Institute of Hematology, School of Medicine, Northwest University, Xi'an 710069, PR China.
⁴ Department of Oncology, The second Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710004, China.
⁵ International Research Laboratory of Glycobiology and Medicinal Chemistry, College of Life Science, Northwest University, Xi'an 710069, PR China. Electronic address: guanfeng@nwu.edu.cn.

PMID: 34000456
DOI: 10.1016/j.jprot.2021.104266

Abstract

Chemoresistance is a major factor driving breast cancer (BC) relapse and the high rates of cancer-related deaths. Aberrant levels of glycans are closely correlated with chemoresistance. The essential functions of glycans in chemoresistance is not systematically studied. In this study, an integrated strategy with a combination of transcriptomics, proteomics, glycomics and glycoproteomics was applied to explore the dysregulation of glycogenes, glycan structures and glycoproteins in chemoresistance of breast cancer cells. In paclitaxel (PTX) resistant MCF7 cells, 19 differentially expressed N-glycan-related proteins were identified, of which MGAT4A was the most significantly down-regulated, consistent with decrease in MGAT4A expression at mRNA level in PTX treated BC cells. Glycomic analysis consistently revealed suppressed levels of multi-antennary branching structures using MALDI-TOF/TOF-MS and lectin microarray. Several target glycoproteins bearing suppressed levels of multi-antennary branching structures were identified, and ERK signaling pathway was strongly suppressed in PTX resistant MCF7 cells. Our findings demonstrated the aberrant levels of multi-antennary branching structures and their target glycoproteins on PTX resistance. Systematically integrative multi-omic analysis is expected to facilitate the discovery of the aberrant glycosyltransferases, N-glycosylation and glycoproteins in tumor progression and chemoresistance. SIGNIFICANCE: An integrated strategy with a combination of transcriptomics, proteomics, glycomics and glycoproteomics is crucial to understand the association between glycans and chemoresistance in BC. In this multi-omic analysis, we identified unique glycan-related protein, glycan and glycoprotein signatures defining PTX chemoresistance in BC. This study might provide valuable information to understand molecular mechanisms underlying chemoresistance in BC.

Keywords: Glycomics; Glycoproteomics; MGAT4A; Multi-antennary; Proteomics; Transcriptomics.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Breast Neoplasms* / drug therapy
Breast Neoplasms* / genetics
Female
Glycomics*
Humans
Paclitaxel / pharmacology
Polysaccharides
Proteomics
Transcriptome

Substances

Polysaccharides
Paclitaxel