Abstract
| Original language | English |
|---|---|
| Pages (from-to) | 649-661 |
| Journal | Journal of Cell Science |
| Volume | 125 |
| Issue number | 3 |
| DOIs | |
| Publication status | Published - 2012 |
| MoE publication type | A1 Journal article-refereed |
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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 journal › Article › Scientific › peer-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 -