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.
authors.affiliation: Medical Biotechnology, VTT Technical Research Centre of Finland, 20521, Turku,  Finland.
authors.forename: Teijo
authors.initials: T
authors.lastname: Pellinen
authors.forename: Juha K
authors.initials: JK
authors.lastname: Rantala
authors.forename: Antti
authors.initials: A
authors.lastname: Arjonen
authors.forename: John-Patrick
authors.initials: JP
authors.lastname: Mpindi
authors.forename: Olli
authors.initials: O
authors.lastname: Kallioniemi
authors.forename: Johanna
authors.initials: J
authors.lastname: Ivaska
mesh_terms: D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D005260:Female; D005786:Gene Expression Regulation; D005820:Genetic Testing / Q000379:methods*; D006801:Humans; D019012:Integrin beta1 / Q000235:genetics* / Q000378:metabolism*; D008297:Male; D020784:Matrix Metalloproteinase 8 / Q000235:genetics / Q000378:metabolism; D046228:Microarray Analysis; D009361:Neoplasm Invasiveness / Q000235:genetics / Q000503:physiopathology; D011471:Prostatic Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D034622:RNA Interference; D060245:Tetraspanin 29 / Q000235:genetics / Q000378:metabolism
chemical_list: C554869:CD9 protein, human; D019012:Integrin beta1; D060245:Tetraspanin 29; C488762:MMP8 protein, human; D020784:Matrix Metalloproteinase 8