Kindlin-2 is expressed in malignant mesothelioma and is required for tumor cell adhesion and migration
Zhengwen An
Unit for Clinical Molecular Biology, Department of Biosciences and Nutrition at Novum, Karolinska Institutet, SE-14183, Stockholm, Sweden
Search for more papers by this authorKatalin Dobra
Department of Laboratory Medicine, Division of Pathology, Karolinska Institutet, SE-14183, Stockholm, Sweden
Search for more papers by this authorJohn G. Lock
Unit for Clinical Molecular Biology, Department of Biosciences and Nutrition at Novum, Karolinska Institutet, SE-14183, Stockholm, Sweden
Search for more papers by this authorStaffan Strömblad
Unit for Clinical Molecular Biology, Department of Biosciences and Nutrition at Novum, Karolinska Institutet, SE-14183, Stockholm, Sweden
Search for more papers by this authorAnders Hjerpe
Department of Laboratory Medicine, Division of Pathology, Karolinska Institutet, SE-14183, Stockholm, Sweden
Search for more papers by this authorCorresponding Author
Hongquan Zhang
Unit for Clinical Molecular Biology, Department of Biosciences and Nutrition at Novum, Karolinska Institutet, SE-14183, Stockholm, Sweden
Peking University School of Basic Medical Sciences, Laboratory of Molecular Cell Biology and Tumor Biology and Key Laboratory of Carcinogenesis and Translational Research, The Ministry of Education, Beijing 100191, People's Republic of China
Tel.: 0046-8-608-9267, Fax: +46-8-608-1501
Department of Biosciences and Nutrition at Novum, Karolinska Institutet, SE-14183, Stockholm, SwedenSearch for more papers by this authorZhengwen An
Unit for Clinical Molecular Biology, Department of Biosciences and Nutrition at Novum, Karolinska Institutet, SE-14183, Stockholm, Sweden
Search for more papers by this authorKatalin Dobra
Department of Laboratory Medicine, Division of Pathology, Karolinska Institutet, SE-14183, Stockholm, Sweden
Search for more papers by this authorJohn G. Lock
Unit for Clinical Molecular Biology, Department of Biosciences and Nutrition at Novum, Karolinska Institutet, SE-14183, Stockholm, Sweden
Search for more papers by this authorStaffan Strömblad
Unit for Clinical Molecular Biology, Department of Biosciences and Nutrition at Novum, Karolinska Institutet, SE-14183, Stockholm, Sweden
Search for more papers by this authorAnders Hjerpe
Department of Laboratory Medicine, Division of Pathology, Karolinska Institutet, SE-14183, Stockholm, Sweden
Search for more papers by this authorCorresponding Author
Hongquan Zhang
Unit for Clinical Molecular Biology, Department of Biosciences and Nutrition at Novum, Karolinska Institutet, SE-14183, Stockholm, Sweden
Peking University School of Basic Medical Sciences, Laboratory of Molecular Cell Biology and Tumor Biology and Key Laboratory of Carcinogenesis and Translational Research, The Ministry of Education, Beijing 100191, People's Republic of China
Tel.: 0046-8-608-9267, Fax: +46-8-608-1501
Department of Biosciences and Nutrition at Novum, Karolinska Institutet, SE-14183, Stockholm, SwedenSearch for more papers by this authorAbstract
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.
Supporting Information
Additional Supporting Information may be found in the online version of this article.
| Filename | Description |
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| IJC_25223_sm_supfig1.tif9.8 MB | Supporting Figure 1 |
| IJC_25223_sm_supfig2.tif5.1 MB | Supporting Figure 2 |
| IJC_25223_sm_supfig3.tif12.5 MB | Supporting Figure 3 |
| IJC_25223_sm_supfig4.tif6.9 MB | Supporting Figure 4 |
| IJC_25223_sm_supfig5.tif5.6 MB | Supporting Figure 5 |
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