Mammary-derived growth inhibitor (MDGI) interacts with integrin α-subunits and suppresses integrin activity and invasion

Jonna Nevo, Anja Mai, Saara Tuomi, Teijo Pellinen, O. T. Pentikäinen, P. Heikkilä, J. Lundin, H. Joensuu, P. Bono, Johanna Ivaska (Corresponding Author)

Research output: Contribution to journalArticleScientificpeer-review

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Abstract

The majority of mortality associated with cancer is due to formation of metastases from the primary tumor. Adhesion mediated by different integrin heterodimers has an important role during cell migration and invasion. Protein interactions with the β1-integrin cytoplasmic tail are known to influence integrin affinity for extracellular ligands, but regulating binding partners for the α-subunit cytoplasmic tails have remained elusive. In this study, we show that mammary-derived growth inhibitor (MDGI) (also known as FABP-3 or H-FABP) binds directly to the cytoplasmic tail of integrin α-subunits and its expression inhibits integrin activity. In breast cancer cell lines, MDGI expression correlates with suppression of the active conformation of integrins. This results in reduced integrin adhesion to type I collagen and fibronectin and inhibition of cell migration and invasion. In tissue microarray of 1331 breast cancer patients, patients with MDGI-positive tumors had more favorable 10-year distant disease-free survival compared with patients with MDGI-negative tumors. Our data indicate that MDGI is a novel interacting partner for integrin α-subunits, and its expression modulates integrin activity and suppresses cell invasion in breast cancer patients. Retained MDGI expression is associated with favorable prognosis.
Original languageEnglish
Pages (from-to)6452-6463
JournalOncogene
Volume29
DOIs
Publication statusPublished - 2010
MoE publication typeA1 Journal article-refereed

Fingerprint

Growth Inhibitors
Integrins
Breast
Breast Neoplasms
Neoplasms
Cell Migration Inhibition
Collagen Type I
Fibronectins
Disease-Free Survival
Cell Movement
Neoplasm Metastasis
Ligands
Cell Line
Mortality

Keywords

  • integrin
  • MDGI
  • breast cancer
  • adhesion
  • migration
  • invasion

Cite this

Nevo, J., Mai, A., Tuomi, S., Pellinen, T., Pentikäinen, O. T., Heikkilä, P., ... Ivaska, J. (2010). Mammary-derived growth inhibitor (MDGI) interacts with integrin α-subunits and suppresses integrin activity and invasion. Oncogene, 29, 6452-6463. https://doi.org/10.1038/onc.2010.376
Nevo, Jonna ; Mai, Anja ; Tuomi, Saara ; Pellinen, Teijo ; Pentikäinen, O. T. ; Heikkilä, P. ; Lundin, J. ; Joensuu, H. ; Bono, P. ; Ivaska, Johanna. / Mammary-derived growth inhibitor (MDGI) interacts with integrin α-subunits and suppresses integrin activity and invasion. In: Oncogene. 2010 ; Vol. 29. pp. 6452-6463.
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abstract = "The majority of mortality associated with cancer is due to formation of metastases from the primary tumor. Adhesion mediated by different integrin heterodimers has an important role during cell migration and invasion. Protein interactions with the β1-integrin cytoplasmic tail are known to influence integrin affinity for extracellular ligands, but regulating binding partners for the α-subunit cytoplasmic tails have remained elusive. In this study, we show that mammary-derived growth inhibitor (MDGI) (also known as FABP-3 or H-FABP) binds directly to the cytoplasmic tail of integrin α-subunits and its expression inhibits integrin activity. In breast cancer cell lines, MDGI expression correlates with suppression of the active conformation of integrins. This results in reduced integrin adhesion to type I collagen and fibronectin and inhibition of cell migration and invasion. In tissue microarray of 1331 breast cancer patients, patients with MDGI-positive tumors had more favorable 10-year distant disease-free survival compared with patients with MDGI-negative tumors. Our data indicate that MDGI is a novel interacting partner for integrin α-subunits, and its expression modulates integrin activity and suppresses cell invasion in breast cancer patients. Retained MDGI expression is associated with favorable prognosis.",
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Nevo, J, Mai, A, Tuomi, S, Pellinen, T, Pentikäinen, OT, Heikkilä, P, Lundin, J, Joensuu, H, Bono, P & Ivaska, J 2010, 'Mammary-derived growth inhibitor (MDGI) interacts with integrin α-subunits and suppresses integrin activity and invasion', Oncogene, vol. 29, pp. 6452-6463. https://doi.org/10.1038/onc.2010.376

Mammary-derived growth inhibitor (MDGI) interacts with integrin α-subunits and suppresses integrin activity and invasion. / Nevo, Jonna; Mai, Anja; Tuomi, Saara; Pellinen, Teijo; Pentikäinen, O. T.; Heikkilä, P.; Lundin, J.; Joensuu, H.; Bono, P.; Ivaska, Johanna (Corresponding Author).

In: Oncogene, Vol. 29, 2010, p. 6452-6463.

Research output: Contribution to journalArticleScientificpeer-review

TY - JOUR

T1 - Mammary-derived growth inhibitor (MDGI) interacts with integrin α-subunits and suppresses integrin activity and invasion

AU - Nevo, Jonna

AU - Mai, Anja

AU - Tuomi, Saara

AU - Pellinen, Teijo

AU - Pentikäinen, O. T.

AU - Heikkilä, P.

AU - Lundin, J.

AU - Joensuu, H.

AU - Bono, P.

AU - Ivaska, Johanna

PY - 2010

Y1 - 2010

N2 - The majority of mortality associated with cancer is due to formation of metastases from the primary tumor. Adhesion mediated by different integrin heterodimers has an important role during cell migration and invasion. Protein interactions with the β1-integrin cytoplasmic tail are known to influence integrin affinity for extracellular ligands, but regulating binding partners for the α-subunit cytoplasmic tails have remained elusive. In this study, we show that mammary-derived growth inhibitor (MDGI) (also known as FABP-3 or H-FABP) binds directly to the cytoplasmic tail of integrin α-subunits and its expression inhibits integrin activity. In breast cancer cell lines, MDGI expression correlates with suppression of the active conformation of integrins. This results in reduced integrin adhesion to type I collagen and fibronectin and inhibition of cell migration and invasion. In tissue microarray of 1331 breast cancer patients, patients with MDGI-positive tumors had more favorable 10-year distant disease-free survival compared with patients with MDGI-negative tumors. Our data indicate that MDGI is a novel interacting partner for integrin α-subunits, and its expression modulates integrin activity and suppresses cell invasion in breast cancer patients. Retained MDGI expression is associated with favorable prognosis.

AB - The majority of mortality associated with cancer is due to formation of metastases from the primary tumor. Adhesion mediated by different integrin heterodimers has an important role during cell migration and invasion. Protein interactions with the β1-integrin cytoplasmic tail are known to influence integrin affinity for extracellular ligands, but regulating binding partners for the α-subunit cytoplasmic tails have remained elusive. In this study, we show that mammary-derived growth inhibitor (MDGI) (also known as FABP-3 or H-FABP) binds directly to the cytoplasmic tail of integrin α-subunits and its expression inhibits integrin activity. In breast cancer cell lines, MDGI expression correlates with suppression of the active conformation of integrins. This results in reduced integrin adhesion to type I collagen and fibronectin and inhibition of cell migration and invasion. In tissue microarray of 1331 breast cancer patients, patients with MDGI-positive tumors had more favorable 10-year distant disease-free survival compared with patients with MDGI-negative tumors. Our data indicate that MDGI is a novel interacting partner for integrin α-subunits, and its expression modulates integrin activity and suppresses cell invasion in breast cancer patients. Retained MDGI expression is associated with favorable prognosis.

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KW - MDGI

KW - breast cancer

KW - adhesion

KW - migration

KW - invasion

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DO - 10.1038/onc.2010.376

M3 - Article

VL - 29

SP - 6452

EP - 6463

JO - Oncogene

JF - Oncogene

SN - 0950-9232

ER -