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Kindlin‐2 is expressed in malignant mesothelioma and is required for tumor cell adhesion and migration
Author(s) -
An Zhengwen,
Dobra Katalin,
Lock John G.,
Strömblad Staffan,
Hjerpe Anders,
Zhang Hongquan
Publication year - 2010
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.25223
Subject(s) - focal adhesion , cancer research , integrin , cell adhesion , microbiology and biotechnology , metastasis , biology , cell migration , cadherin , cell growth , cell , cancer , signal transduction , genetics
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.