A functional genetic screen reveals new regulators of β1-integrin activity

Teijo Pellinen, Juha K. Rantala, Antti Arjonen, John-Patrick Mpindi, Olli Kallioniemi, Johanna Ivaska (Corresponding Author)

Research output: Contribution to journalArticleScientificpeer-review

28 Citations (Scopus)

Abstract

β1 integrins constitute a large group of widely distributed adhesion receptors, which regulate the ability of cells to interact with their surroundings. This regulation of the expression and activity of integrins is crucial for tissue homeostasis and development and contributes to inflammation and cancer. We report an RNA interference screen to uncover genes involved in the regulation of β1-integrin activity using cell spot microarray technology in cancer cell lines. Altogether, ten cancer and two normal cell lines were used to identify regulators of β1 integrin activity. Cell biological analysis of the identified β1-integrin regulatory genes revealed that modulation of integrin activity can influence cell invasion in a three-dimensional matrix. We demonstrate with loss-of-function and rescue experiments that CD9 activates and MMP8 inactivates β1 integrins and that both proteins associate with β1 integrins in cells. Furthermore, CD9 and MMP8 regulate cancer cell extravasation in vivo. Our discovery of new regulators of β1-integrin activity highlight the complexity of integrin activity regulation and provide a set of new genes involved in regulation of integrin function.
Original languageEnglish
Pages (from-to)649-661
JournalJournal of Cell Science
Volume125
Issue number3
DOIs
Publication statusPublished - 2012
MoE publication typeA1 Journal article-refereed

Fingerprint

Integrins
Neoplasms
Cell Line
Regulator Genes
RNA Interference
Genes
Homeostasis
Inflammation
Technology

Cite this

Pellinen, T., Rantala, J. K., Arjonen, A., Mpindi, J-P., Kallioniemi, O., & Ivaska, J. (2012). A functional genetic screen reveals new regulators of β1-integrin activity. Journal of Cell Science, 125(3), 649-661. https://doi.org/10.1242/jcs.090704
Pellinen, Teijo ; Rantala, Juha K. ; Arjonen, Antti ; Mpindi, John-Patrick ; Kallioniemi, Olli ; Ivaska, Johanna. / A functional genetic screen reveals new regulators of β1-integrin activity. In: Journal of Cell Science. 2012 ; Vol. 125, No. 3. pp. 649-661.
@article{eb29e0592fb54ae7af64a86b9b6552e8,
title = "A functional genetic screen reveals new regulators of β1-integrin activity",
abstract = "β1 integrins constitute a large group of widely distributed adhesion receptors, which regulate the ability of cells to interact with their surroundings. This regulation of the expression and activity of integrins is crucial for tissue homeostasis and development and contributes to inflammation and cancer. We report an RNA interference screen to uncover genes involved in the regulation of β1-integrin activity using cell spot microarray technology in cancer cell lines. Altogether, ten cancer and two normal cell lines were used to identify regulators of β1 integrin activity. Cell biological analysis of the identified β1-integrin regulatory genes revealed that modulation of integrin activity can influence cell invasion in a three-dimensional matrix. We demonstrate with loss-of-function and rescue experiments that CD9 activates and MMP8 inactivates β1 integrins and that both proteins associate with β1 integrins in cells. Furthermore, CD9 and MMP8 regulate cancer cell extravasation in vivo. Our discovery of new regulators of β1-integrin activity highlight the complexity of integrin activity regulation and provide a set of new genes involved in regulation of integrin function.",
author = "Teijo Pellinen and Rantala, {Juha K.} and Antti Arjonen and John-Patrick Mpindi and Olli Kallioniemi and Johanna Ivaska",
year = "2012",
doi = "10.1242/jcs.090704",
language = "English",
volume = "125",
pages = "649--661",
journal = "Journal of Cell Science",
issn = "0021-9533",
publisher = "Company of Biologists Ltd",
number = "3",

}

Pellinen, T, Rantala, JK, Arjonen, A, Mpindi, J-P, Kallioniemi, O & Ivaska, J 2012, 'A functional genetic screen reveals new regulators of β1-integrin activity', Journal of Cell Science, vol. 125, no. 3, pp. 649-661. https://doi.org/10.1242/jcs.090704

A functional genetic screen reveals new regulators of β1-integrin activity. / Pellinen, Teijo; Rantala, Juha K.; Arjonen, Antti; Mpindi, John-Patrick; Kallioniemi, Olli; Ivaska, Johanna (Corresponding Author).

In: Journal of Cell Science, Vol. 125, No. 3, 2012, p. 649-661.

Research output: Contribution to journalArticleScientificpeer-review

TY - JOUR

T1 - A functional genetic screen reveals new regulators of β1-integrin activity

AU - Pellinen, Teijo

AU - Rantala, Juha K.

AU - Arjonen, Antti

AU - Mpindi, John-Patrick

AU - Kallioniemi, Olli

AU - Ivaska, Johanna

PY - 2012

Y1 - 2012

N2 - β1 integrins constitute a large group of widely distributed adhesion receptors, which regulate the ability of cells to interact with their surroundings. This regulation of the expression and activity of integrins is crucial for tissue homeostasis and development and contributes to inflammation and cancer. We report an RNA interference screen to uncover genes involved in the regulation of β1-integrin activity using cell spot microarray technology in cancer cell lines. Altogether, ten cancer and two normal cell lines were used to identify regulators of β1 integrin activity. Cell biological analysis of the identified β1-integrin regulatory genes revealed that modulation of integrin activity can influence cell invasion in a three-dimensional matrix. We demonstrate with loss-of-function and rescue experiments that CD9 activates and MMP8 inactivates β1 integrins and that both proteins associate with β1 integrins in cells. Furthermore, CD9 and MMP8 regulate cancer cell extravasation in vivo. Our discovery of new regulators of β1-integrin activity highlight the complexity of integrin activity regulation and provide a set of new genes involved in regulation of integrin function.

AB - β1 integrins constitute a large group of widely distributed adhesion receptors, which regulate the ability of cells to interact with their surroundings. This regulation of the expression and activity of integrins is crucial for tissue homeostasis and development and contributes to inflammation and cancer. We report an RNA interference screen to uncover genes involved in the regulation of β1-integrin activity using cell spot microarray technology in cancer cell lines. Altogether, ten cancer and two normal cell lines were used to identify regulators of β1 integrin activity. Cell biological analysis of the identified β1-integrin regulatory genes revealed that modulation of integrin activity can influence cell invasion in a three-dimensional matrix. We demonstrate with loss-of-function and rescue experiments that CD9 activates and MMP8 inactivates β1 integrins and that both proteins associate with β1 integrins in cells. Furthermore, CD9 and MMP8 regulate cancer cell extravasation in vivo. Our discovery of new regulators of β1-integrin activity highlight the complexity of integrin activity regulation and provide a set of new genes involved in regulation of integrin function.

U2 - 10.1242/jcs.090704

DO - 10.1242/jcs.090704

M3 - Article

VL - 125

SP - 649

EP - 661

JO - Journal of Cell Science

JF - Journal of Cell Science

SN - 0021-9533

IS - 3

ER -

Pellinen T, Rantala JK, Arjonen A, Mpindi J-P, Kallioniemi O, Ivaska J. A functional genetic screen reveals new regulators of β1-integrin activity. Journal of Cell Science. 2012;125(3):649-661. https://doi.org/10.1242/jcs.090704