Syndecan-1 and -4 differentially regulate oncogenic K-ras dependent cell invasion into collagen through α2β1 integrin and MT1-MMP

Karoliina Vuoriluoto, Gunilla Högnäs, Pipsa Meller, Kaisa Lehti, Johanna Ivaska (Corresponding Author)

Research output: Contribution to journalArticleScientificpeer-review

29 Citations (Scopus)

Abstract

Syndecans function as co-receptors for integrins on different matrixes. Recently, syndecan-1 has been shown to be important for α2β1 integrin-mediated adhesion to collagen in tumor cells by regulating cell adhesion and migration on two-dimensional collagen. However, the function of syndecans in supporting α2β1 integrin interactions with three-dimensional (3D) collagen is less well studied. Using loss-of-function and overexpression experiments we show that in 3D collagen syndecan-4 supports α2β1-mediated collagen matrix contraction. Cell invasion through type I collagen containing 3D extracellular matrix (ECM) is driven by α2β1 integrin and membrane type-1 matrix metalloproteinase (MT1-MMP). Here we show that mutational activation of K-ras correlates with increased expression of α2β1 integrin, MT1-MMP, syndecan-1, and syndecan-4. While K-ras-induced α2β1 integrin and MT1-MMP are positive regulators of invasion, silencing and overexpression of syndecans demonstrate that these proteins inhibit cell invasion into collagen. Taken together, these data demonstrate the existence of a complex interplay between integrin α2β1, MT1-MMP, and syndecans in the invasion of K-ras mutant cells in 3D collagen that may represent a mechanism by which tumor cells become more invasive and metastatic.
Original languageEnglish
Pages (from-to)207-217
JournalMatrix Biology
Volume30
Issue number3
DOIs
Publication statusPublished - 2011
MoE publication typeA1 Journal article-refereed

Fingerprint

Syndecan-4
Syndecan-1
Matrix Metalloproteinase 14
Integrins
Syndecans
Collagen
Collagen Type I
Cell Adhesion
Cell Movement
Extracellular Matrix
Neoplasms

Keywords

  • K-ras
  • Integrin
  • MT1-MMP
  • Syndecan
  • Invasion
  • Contraction

Cite this

Vuoriluoto, Karoliina ; Högnäs, Gunilla ; Meller, Pipsa ; Lehti, Kaisa ; Ivaska, Johanna. / Syndecan-1 and -4 differentially regulate oncogenic K-ras dependent cell invasion into collagen through α2β1 integrin and MT1-MMP. In: Matrix Biology. 2011 ; Vol. 30, No. 3. pp. 207-217.
@article{00ba68c3c5ad433fb6f905c7d03b4a10,
title = "Syndecan-1 and -4 differentially regulate oncogenic K-ras dependent cell invasion into collagen through α2β1 integrin and MT1-MMP",
abstract = "Syndecans function as co-receptors for integrins on different matrixes. Recently, syndecan-1 has been shown to be important for α2β1 integrin-mediated adhesion to collagen in tumor cells by regulating cell adhesion and migration on two-dimensional collagen. However, the function of syndecans in supporting α2β1 integrin interactions with three-dimensional (3D) collagen is less well studied. Using loss-of-function and overexpression experiments we show that in 3D collagen syndecan-4 supports α2β1-mediated collagen matrix contraction. Cell invasion through type I collagen containing 3D extracellular matrix (ECM) is driven by α2β1 integrin and membrane type-1 matrix metalloproteinase (MT1-MMP). Here we show that mutational activation of K-ras correlates with increased expression of α2β1 integrin, MT1-MMP, syndecan-1, and syndecan-4. While K-ras-induced α2β1 integrin and MT1-MMP are positive regulators of invasion, silencing and overexpression of syndecans demonstrate that these proteins inhibit cell invasion into collagen. Taken together, these data demonstrate the existence of a complex interplay between integrin α2β1, MT1-MMP, and syndecans in the invasion of K-ras mutant cells in 3D collagen that may represent a mechanism by which tumor cells become more invasive and metastatic.",
keywords = "K-ras, Integrin, MT1-MMP, Syndecan, Invasion, Contraction",
author = "Karoliina Vuoriluoto and Gunilla H{\"o}gn{\"a}s and Pipsa Meller and Kaisa Lehti and Johanna Ivaska",
year = "2011",
doi = "10.1016/j.matbio.2011.03.003",
language = "English",
volume = "30",
pages = "207--217",
journal = "Matrix Biology",
issn = "0945-053X",
publisher = "Elsevier",
number = "3",

}

Syndecan-1 and -4 differentially regulate oncogenic K-ras dependent cell invasion into collagen through α2β1 integrin and MT1-MMP. / Vuoriluoto, Karoliina; Högnäs, Gunilla; Meller, Pipsa; Lehti, Kaisa; Ivaska, Johanna (Corresponding Author).

In: Matrix Biology, Vol. 30, No. 3, 2011, p. 207-217.

Research output: Contribution to journalArticleScientificpeer-review

TY - JOUR

T1 - Syndecan-1 and -4 differentially regulate oncogenic K-ras dependent cell invasion into collagen through α2β1 integrin and MT1-MMP

AU - Vuoriluoto, Karoliina

AU - Högnäs, Gunilla

AU - Meller, Pipsa

AU - Lehti, Kaisa

AU - Ivaska, Johanna

PY - 2011

Y1 - 2011

N2 - Syndecans function as co-receptors for integrins on different matrixes. Recently, syndecan-1 has been shown to be important for α2β1 integrin-mediated adhesion to collagen in tumor cells by regulating cell adhesion and migration on two-dimensional collagen. However, the function of syndecans in supporting α2β1 integrin interactions with three-dimensional (3D) collagen is less well studied. Using loss-of-function and overexpression experiments we show that in 3D collagen syndecan-4 supports α2β1-mediated collagen matrix contraction. Cell invasion through type I collagen containing 3D extracellular matrix (ECM) is driven by α2β1 integrin and membrane type-1 matrix metalloproteinase (MT1-MMP). Here we show that mutational activation of K-ras correlates with increased expression of α2β1 integrin, MT1-MMP, syndecan-1, and syndecan-4. While K-ras-induced α2β1 integrin and MT1-MMP are positive regulators of invasion, silencing and overexpression of syndecans demonstrate that these proteins inhibit cell invasion into collagen. Taken together, these data demonstrate the existence of a complex interplay between integrin α2β1, MT1-MMP, and syndecans in the invasion of K-ras mutant cells in 3D collagen that may represent a mechanism by which tumor cells become more invasive and metastatic.

AB - Syndecans function as co-receptors for integrins on different matrixes. Recently, syndecan-1 has been shown to be important for α2β1 integrin-mediated adhesion to collagen in tumor cells by regulating cell adhesion and migration on two-dimensional collagen. However, the function of syndecans in supporting α2β1 integrin interactions with three-dimensional (3D) collagen is less well studied. Using loss-of-function and overexpression experiments we show that in 3D collagen syndecan-4 supports α2β1-mediated collagen matrix contraction. Cell invasion through type I collagen containing 3D extracellular matrix (ECM) is driven by α2β1 integrin and membrane type-1 matrix metalloproteinase (MT1-MMP). Here we show that mutational activation of K-ras correlates with increased expression of α2β1 integrin, MT1-MMP, syndecan-1, and syndecan-4. While K-ras-induced α2β1 integrin and MT1-MMP are positive regulators of invasion, silencing and overexpression of syndecans demonstrate that these proteins inhibit cell invasion into collagen. Taken together, these data demonstrate the existence of a complex interplay between integrin α2β1, MT1-MMP, and syndecans in the invasion of K-ras mutant cells in 3D collagen that may represent a mechanism by which tumor cells become more invasive and metastatic.

KW - K-ras

KW - Integrin

KW - MT1-MMP

KW - Syndecan

KW - Invasion

KW - Contraction

U2 - 10.1016/j.matbio.2011.03.003

DO - 10.1016/j.matbio.2011.03.003

M3 - Article

VL - 30

SP - 207

EP - 217

JO - Matrix Biology

JF - Matrix Biology

SN - 0945-053X

IS - 3

ER -