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 language | English |
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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 |