Contribution of Membrane Mucins to Tumor Progression Through Modulation of Cellular Growth Signaling Pathways

Kermit L Carraway, Melanie Funes, Heather C. Workman, Colleen A Sweeney

Research output: Contribution to journalArticle

63 Citations (Scopus)

Abstract

Mucins are large, heavily O-glycosylated proteins expressed by epithelial tissues. The canonical function of membrane mucins is to provide protection to vulnerable epithelia by forming a steric barrier against assault, and by contributing to the formation of protective extracellular mucin gels. The aberrant overexpression of mucins is thought to contribute to tumor progression by allowing tumor cells to evade immune recognition, and by aiding in the breakdown of cell-cell and cell-matrix contacts to facilitate migration and metastasis. Recent evidence suggests that we should now modify our thinking about mucin function by considering their roles in signaling pathways leading to cellular growth control. Here we review the markedly divergent mechanisms by which membrane mucins, specifically MUC1 and MUC4, influence pathways contributing to cellular proliferation and survival. The cytoplasmic domain of MUC1 serves as a scaffold for the assembly of a variety of signaling proteins, while MUC4 influences the trafficking and localization of growth factor receptors, and hence their responses to external stimuli. We also discuss how tumor cells exploit these mechanisms to promote their own growth and metastasis.

Original languageEnglish (US)
Pages (from-to)1-22
Number of pages22
JournalCurrent Topics in Developmental Biology
Volume78
DOIs
StatePublished - 2007

Fingerprint

Mucins
Membranes
Growth
Neoplasms
Epithelium
Neoplasm Metastasis
Growth Factor Receptors
Proteins
Gels
Cell Proliferation

ASJC Scopus subject areas

  • Developmental Biology

Cite this

@article{151657f085c649f695e312105d938ea6,
title = "Contribution of Membrane Mucins to Tumor Progression Through Modulation of Cellular Growth Signaling Pathways",
abstract = "Mucins are large, heavily O-glycosylated proteins expressed by epithelial tissues. The canonical function of membrane mucins is to provide protection to vulnerable epithelia by forming a steric barrier against assault, and by contributing to the formation of protective extracellular mucin gels. The aberrant overexpression of mucins is thought to contribute to tumor progression by allowing tumor cells to evade immune recognition, and by aiding in the breakdown of cell-cell and cell-matrix contacts to facilitate migration and metastasis. Recent evidence suggests that we should now modify our thinking about mucin function by considering their roles in signaling pathways leading to cellular growth control. Here we review the markedly divergent mechanisms by which membrane mucins, specifically MUC1 and MUC4, influence pathways contributing to cellular proliferation and survival. The cytoplasmic domain of MUC1 serves as a scaffold for the assembly of a variety of signaling proteins, while MUC4 influences the trafficking and localization of growth factor receptors, and hence their responses to external stimuli. We also discuss how tumor cells exploit these mechanisms to promote their own growth and metastasis.",
author = "Carraway, {Kermit L} and Melanie Funes and Workman, {Heather C.} and Sweeney, {Colleen A}",
year = "2007",
doi = "10.1016/S0070-2153(06)78001-2",
language = "English (US)",
volume = "78",
pages = "1--22",
journal = "Current Topics in Developmental Biology",
issn = "0070-2153",
publisher = "Academic Press Inc.",

}

TY - JOUR

T1 - Contribution of Membrane Mucins to Tumor Progression Through Modulation of Cellular Growth Signaling Pathways

AU - Carraway, Kermit L

AU - Funes, Melanie

AU - Workman, Heather C.

AU - Sweeney, Colleen A

PY - 2007

Y1 - 2007

N2 - Mucins are large, heavily O-glycosylated proteins expressed by epithelial tissues. The canonical function of membrane mucins is to provide protection to vulnerable epithelia by forming a steric barrier against assault, and by contributing to the formation of protective extracellular mucin gels. The aberrant overexpression of mucins is thought to contribute to tumor progression by allowing tumor cells to evade immune recognition, and by aiding in the breakdown of cell-cell and cell-matrix contacts to facilitate migration and metastasis. Recent evidence suggests that we should now modify our thinking about mucin function by considering their roles in signaling pathways leading to cellular growth control. Here we review the markedly divergent mechanisms by which membrane mucins, specifically MUC1 and MUC4, influence pathways contributing to cellular proliferation and survival. The cytoplasmic domain of MUC1 serves as a scaffold for the assembly of a variety of signaling proteins, while MUC4 influences the trafficking and localization of growth factor receptors, and hence their responses to external stimuli. We also discuss how tumor cells exploit these mechanisms to promote their own growth and metastasis.

AB - Mucins are large, heavily O-glycosylated proteins expressed by epithelial tissues. The canonical function of membrane mucins is to provide protection to vulnerable epithelia by forming a steric barrier against assault, and by contributing to the formation of protective extracellular mucin gels. The aberrant overexpression of mucins is thought to contribute to tumor progression by allowing tumor cells to evade immune recognition, and by aiding in the breakdown of cell-cell and cell-matrix contacts to facilitate migration and metastasis. Recent evidence suggests that we should now modify our thinking about mucin function by considering their roles in signaling pathways leading to cellular growth control. Here we review the markedly divergent mechanisms by which membrane mucins, specifically MUC1 and MUC4, influence pathways contributing to cellular proliferation and survival. The cytoplasmic domain of MUC1 serves as a scaffold for the assembly of a variety of signaling proteins, while MUC4 influences the trafficking and localization of growth factor receptors, and hence their responses to external stimuli. We also discuss how tumor cells exploit these mechanisms to promote their own growth and metastasis.

UR - http://www.scopus.com/inward/record.url?scp=33847328331&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=33847328331&partnerID=8YFLogxK

U2 - 10.1016/S0070-2153(06)78001-2

DO - 10.1016/S0070-2153(06)78001-2

M3 - Article

VL - 78

SP - 1

EP - 22

JO - Current Topics in Developmental Biology

JF - Current Topics in Developmental Biology

SN - 0070-2153

ER -