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Proteomic analysis of O-GlcNAcylated proteins in invasive ductal breast carcinomas with and without lymph node metastasis

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Abstract

The potential role of protein O-GlcNAcylation in cancer has been studied extensively, and the spread of cancer cells to regional lymph nodes is the first step in the dissemination of breast cancer. However, the correlation between O-GlcNAcylation and lymphatic metastasis in breast cancer remains elusive. In this study, we demonstrated that the overall O-GlcNAcylation as well as O-GlcNAc transferase (OGT) tends to decrease in response to the augmentation of lymph node metastasis (LNM) in invasive ductal breast carcinomas (IDCs). Although accumulating evidence indicates that individual O-GlcNAcylation may be important in the pathogenesis of breast cancer, O-GlcNAcylated proteins in IDCs are still largely unexplored. Herein, O-GlcNAcylated proteins of IDCs were chemo-enzymatically enriched and identified via liquid chromatography combined with tandem mass spectrometry. In total, 155 O-GlcNAcylated proteins were determined, of which 41 were only observed in LNM tissues, while 40 were unique in non-LNM samples. Gene ontology analysis showed that O-GlcNAc is primarily a nucleocytoplasmic post-translational modification, and most enriched functional terms were related to cancer development in both metastatic and non-metastatic IDCs. Moreover, several O-GlcNAcylated proteins involved in glycolysis and its accessory pathway were identified from LNM and non-LNM groups, respectively. These results indicate that the O-GlcNAcylation statuses of individual proteins were independent of the overall O-GlcNAcylation levels of metastatic and non-metastatic IDCs. Aberrant O-GlcNAc modification of these proteins might be associated with LNM progression.

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Abbreviations

OGT:

O-GlcNAc transferase

OGA:

O-GlcNAcase

IDC:

Invasive ductal breast carcinoma

LNM:

Lymph node metastasis

LC–MS/MS:

Liquid chromatography coupled with tandem mass spectrometry

O-GlcNAc:

O-linked β-D-N-acetylglucosamine

PPP:

Pentose phosphate pathway

TAMRA:

Tetramethylrhodamine

HSPA6:

Heat shock 70 kDa protein 6

eEF1A:

Elongation factor 1-alpha 1

ENO1:

Enolase 1

FBP1:

Fructose-1,6-bisphosphatase 1

ALDOB:

Aldolase B

TKT:

Transketolase

TALDO1:

Transaldolase 1

TPI1:

Triosephosphate isomerase 1

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Acknowledgments

This work was financially supported by the National Basic Research Program of China (973 Program, Grant No. 2012CB910303, 2012CB910301 and 2011CB910603) and National Natural Science Foundation of China (31470795, 31170768).

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Authors and Affiliations

  1. State Key Laboratory of Medicinal Chemical Biology and College of Pharmacy, Collaborative Innovation Center for Biotherapy, and Tianjin Key Laboratory of Molecular Drug Research, Nankai University, Tianjin, 300071, China

    Kuan Jiang, Ling Li, Bingyang Bai, Peng George Wang & Lianwen Zhang

  2. School of Medicine, Nankai University, Tianjin, 300071, China

    Yang Gao

  3. Department of Pathology, The Central Hospital of Taian, 29 Longtan Road, Taian, 271000, China

    Weiwei Hou & Gang Hou

  4. State Key Laboratory of Proteomics, Beijing Proteome Research Center, Beijing Institute of Radiation Medicine, Beijing, 102206, China

    Fang Tian & Wantao Ying

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  1. Kuan Jiang
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  2. Yang Gao
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  3. Weiwei Hou
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  4. Fang Tian
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  6. Ling Li
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  8. Gang Hou
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  9. Peng George Wang
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  10. Lianwen Zhang
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Correspondence to Gang Hou, Peng George Wang or Lianwen Zhang.

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Handling Editor: P. R. Jungblut.

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Jiang, K., Gao, Y., Hou, W. et al. Proteomic analysis of O-GlcNAcylated proteins in invasive ductal breast carcinomas with and without lymph node metastasis. Amino Acids 48, 365–374 (2016). https://doi.org/10.1007/s00726-015-2089-8

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  • DOI: https://doi.org/10.1007/s00726-015-2089-8

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