title: Kindlin-2 is expressed in malignant mesothelioma and is required for tumor cell adhesion and migration.
abstract: Kindlin-2 is a novel integrin-interacting focal adhesion protein that belongs to the Kindlin family. Focal adhesion proteins control cytoskeleton dynamics and promote cancer cell growth, survival, migration and metastasis. Little is known, however, about expression of Kindlin-2 in association with human cancer. We now reveal high Kindlin-2 expression in malignant mesothelioma (MM) cell lines using an affinity-purified anti-Kindlin-2 antibody. Furthermore, we show by immunohistochemistry that Kindlin-2 is highly expressed in 92 of 102 (90%) MMs with epitheliod; sarcomatoid, biphasic and poorly differentiated morphologies. In addition, Kindlin-2 expression correlates to cell proliferation, suggesting a role for Kindlin-2 in tumor growth. We also detect increased expression of Kindlin-2 at the invasion front of tumors concurrent with increased expression of integrin-linked kinase, a Kindlin-binding protein. Besides the high expression of Kindlin-2 in pleural MMs, pleural metastases of lung adenocarcinoma also express large amounts of Kindlin-2, but not Kindlin-1. Notably, in vitro, when endogenous Kindlin-2 was knocked down with RNAi in MM cells, this impaired cell spreading, adhesion and migration. Overall, our study suggests that heightened expression of Kindlin-2 might contribute to tumor progression in MM.
authors.affiliation: Unit for Clinical Molecular Biology, Department of Biosciences and Nutrition at Novum, Karolinska Institutet, SE-14183, Stockholm, Sweden.
authors.forename: Zhengwen
authors.initials: Z
authors.lastname: An
authors.forename: Katalin
authors.initials: K
authors.lastname: Dobra
authors.forename: John G
authors.initials: JG
authors.lastname: Lock
authors.forename: Staffan
authors.initials: S
authors.lastname: Strömblad
authors.forename: Anders
authors.initials: A
authors.lastname: Hjerpe
authors.forename: Hongquan
authors.initials: H
authors.lastname: Zhang
mesh_terms: D002448:Cell Adhesion; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D018450:Disease Progression; D006801:Humans; D008175:Lung Neoplasms / Q000378:metabolism*; D008565:Membrane Proteins / Q000378:metabolism*; D008654:Mesothelioma / Q000378:metabolism*; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D009363:Neoplasm Proteins / Q000378:metabolism*; D010997:Pleural Neoplasms / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D000099200:Scaffold Protein ILK
chemical_list: D008565:Membrane Proteins; D009363:Neoplasm Proteins; D017346:Protein Serine-Threonine Kinases; D000099200:Scaffold Protein ILK; C475301:FERMT1 protein, human; C477322:FERMT3 protein, human