The bisecting GlcNAc on N-glycans inhibits growth factor signaling and retards mammary tumor progression

Yinghui Song, Jason A. Aglipay, Joshua D. Bernstein, Sumanta Goswami, Pamela Stanley

Research output: Contribution to journalArticle

61 Citations (Scopus)

Abstract

The branching of complex N-glycans attached to growth factor receptors promotes tumor progression by prolonging growth factor signaling. The addition of the bisecting GlcNAc to complex N-glycans by Mgat3 has varying effects on cell adhesion, cell migration, and hepatoma formation. Here, we show that Chinese hamster ovary cells expressing Mgat3 and the polyoma middle T (PyMT) antigen have reduced cell proliferation and growth factor signaling dependent on a galectin lattice. The Mgat3 gene is not expressed in virgin mammary gland but is upregulated during lactation and is expressed in mouse mammary tumor virus (MMTV)/PyMT tumors. Mice lacking Mgat3 that cannot transfer the bisecting GlcNAc to N-glycans acquire PyMT-induced mammary tumors more rapidly and have an increased tumor burden, increased migration of tumor cells, and increased early metastasis to lung. Tumors and tumor-derived cells lacking Mgat3 exhibit enhanced signaling through the Ras pathway and reduced amounts of functionally glycosylated α-dystroglycan. Constitutive overexpression of an MMTV/Mgat3 transgene inhibits early mammary tumor development and tumor cell migration. Thus, the addition of the bisecting GlcNAc to complex N-glycans of mammary tumor cell glycoprotein receptors is a cell autonomous mechanism serving to retard tumor progression by reducing growth factor signaling.

Original languageEnglish (US)
Pages (from-to)3361-3371
Number of pages11
JournalCancer Research
Volume70
Issue number8
DOIs
StatePublished - Apr 15 2010

Fingerprint

Polysaccharides
Intercellular Signaling Peptides and Proteins
Breast Neoplasms
Neoplasms
Cell Movement
Mouse mammary tumor virus
Dystroglycans
Galectins
Growth Factor Receptors
Viral Tumor Antigens
Human Mammary Glands
Cricetulus
Tumor Burden
Transgenes
Lactation
Cell Adhesion
Hepatocellular Carcinoma
Ovary
Glycoproteins
Cell Proliferation

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

The bisecting GlcNAc on N-glycans inhibits growth factor signaling and retards mammary tumor progression. / Song, Yinghui; Aglipay, Jason A.; Bernstein, Joshua D.; Goswami, Sumanta; Stanley, Pamela.

In: Cancer Research, Vol. 70, No. 8, 15.04.2010, p. 3361-3371.

Research output: Contribution to journalArticle

Song, Yinghui ; Aglipay, Jason A. ; Bernstein, Joshua D. ; Goswami, Sumanta ; Stanley, Pamela. / The bisecting GlcNAc on N-glycans inhibits growth factor signaling and retards mammary tumor progression. In: Cancer Research. 2010 ; Vol. 70, No. 8. pp. 3361-3371.
@article{26d8901ae9994044b5ce4f8141f1a312,
title = "The bisecting GlcNAc on N-glycans inhibits growth factor signaling and retards mammary tumor progression",
abstract = "The branching of complex N-glycans attached to growth factor receptors promotes tumor progression by prolonging growth factor signaling. The addition of the bisecting GlcNAc to complex N-glycans by Mgat3 has varying effects on cell adhesion, cell migration, and hepatoma formation. Here, we show that Chinese hamster ovary cells expressing Mgat3 and the polyoma middle T (PyMT) antigen have reduced cell proliferation and growth factor signaling dependent on a galectin lattice. The Mgat3 gene is not expressed in virgin mammary gland but is upregulated during lactation and is expressed in mouse mammary tumor virus (MMTV)/PyMT tumors. Mice lacking Mgat3 that cannot transfer the bisecting GlcNAc to N-glycans acquire PyMT-induced mammary tumors more rapidly and have an increased tumor burden, increased migration of tumor cells, and increased early metastasis to lung. Tumors and tumor-derived cells lacking Mgat3 exhibit enhanced signaling through the Ras pathway and reduced amounts of functionally glycosylated α-dystroglycan. Constitutive overexpression of an MMTV/Mgat3 transgene inhibits early mammary tumor development and tumor cell migration. Thus, the addition of the bisecting GlcNAc to complex N-glycans of mammary tumor cell glycoprotein receptors is a cell autonomous mechanism serving to retard tumor progression by reducing growth factor signaling.",
author = "Yinghui Song and Aglipay, {Jason A.} and Bernstein, {Joshua D.} and Sumanta Goswami and Pamela Stanley",
year = "2010",
month = "4",
day = "15",
doi = "10.1158/0008-5472.CAN-09-2719",
language = "English (US)",
volume = "70",
pages = "3361--3371",
journal = "Cancer Research",
issn = "0008-5472",
publisher = "American Association for Cancer Research Inc.",
number = "8",

}

TY - JOUR

T1 - The bisecting GlcNAc on N-glycans inhibits growth factor signaling and retards mammary tumor progression

AU - Song, Yinghui

AU - Aglipay, Jason A.

AU - Bernstein, Joshua D.

AU - Goswami, Sumanta

AU - Stanley, Pamela

PY - 2010/4/15

Y1 - 2010/4/15

N2 - The branching of complex N-glycans attached to growth factor receptors promotes tumor progression by prolonging growth factor signaling. The addition of the bisecting GlcNAc to complex N-glycans by Mgat3 has varying effects on cell adhesion, cell migration, and hepatoma formation. Here, we show that Chinese hamster ovary cells expressing Mgat3 and the polyoma middle T (PyMT) antigen have reduced cell proliferation and growth factor signaling dependent on a galectin lattice. The Mgat3 gene is not expressed in virgin mammary gland but is upregulated during lactation and is expressed in mouse mammary tumor virus (MMTV)/PyMT tumors. Mice lacking Mgat3 that cannot transfer the bisecting GlcNAc to N-glycans acquire PyMT-induced mammary tumors more rapidly and have an increased tumor burden, increased migration of tumor cells, and increased early metastasis to lung. Tumors and tumor-derived cells lacking Mgat3 exhibit enhanced signaling through the Ras pathway and reduced amounts of functionally glycosylated α-dystroglycan. Constitutive overexpression of an MMTV/Mgat3 transgene inhibits early mammary tumor development and tumor cell migration. Thus, the addition of the bisecting GlcNAc to complex N-glycans of mammary tumor cell glycoprotein receptors is a cell autonomous mechanism serving to retard tumor progression by reducing growth factor signaling.

AB - The branching of complex N-glycans attached to growth factor receptors promotes tumor progression by prolonging growth factor signaling. The addition of the bisecting GlcNAc to complex N-glycans by Mgat3 has varying effects on cell adhesion, cell migration, and hepatoma formation. Here, we show that Chinese hamster ovary cells expressing Mgat3 and the polyoma middle T (PyMT) antigen have reduced cell proliferation and growth factor signaling dependent on a galectin lattice. The Mgat3 gene is not expressed in virgin mammary gland but is upregulated during lactation and is expressed in mouse mammary tumor virus (MMTV)/PyMT tumors. Mice lacking Mgat3 that cannot transfer the bisecting GlcNAc to N-glycans acquire PyMT-induced mammary tumors more rapidly and have an increased tumor burden, increased migration of tumor cells, and increased early metastasis to lung. Tumors and tumor-derived cells lacking Mgat3 exhibit enhanced signaling through the Ras pathway and reduced amounts of functionally glycosylated α-dystroglycan. Constitutive overexpression of an MMTV/Mgat3 transgene inhibits early mammary tumor development and tumor cell migration. Thus, the addition of the bisecting GlcNAc to complex N-glycans of mammary tumor cell glycoprotein receptors is a cell autonomous mechanism serving to retard tumor progression by reducing growth factor signaling.

UR - http://www.scopus.com/inward/record.url?scp=77951072143&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=77951072143&partnerID=8YFLogxK

U2 - 10.1158/0008-5472.CAN-09-2719

DO - 10.1158/0008-5472.CAN-09-2719

M3 - Article

C2 - 20395209

AN - SCOPUS:77951072143

VL - 70

SP - 3361

EP - 3371

JO - Cancer Research

JF - Cancer Research

SN - 0008-5472

IS - 8

ER -