期刊
INTERNATIONAL JOURNAL OF CANCER
卷 127, 期 9, 页码 1999-2008出版社
WILEY-BLACKWELL
DOI: 10.1002/ijc.25223
关键词
Kindlin-2; malignant mesothelioma; adhesion and migration; tumor progression
类别
资金
- Swedish Cancer Foundation
- Swedish Society of Medicine
- Swedish Research Council
- Heart Lung funds
- AFA insurance research funds
- Karolinska Institute funds
- Peking University
- Nature Science Foundation of China [30830048]
- Ministry of Science and Technology of China [201003912203]
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.
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