Abstract
Epithelial–mesenchymal transition (EMT) plays a pivotal role for tumor progression. Recent studies have revealed the existence of distinct intermediate states in EMT (partial EMT); however, the mechanisms underlying partial EMT are not fully understood. Here, we demonstrate that αvβ3 integrin induces partial EMT, which is characterized by acquiring mesenchymal phenotypes while retaining epithelial markers. We found αvβ3 integrin to be associated with poor survival in patients with lung adenocarcinoma. Moreover, αvβ3 integrin-induced partial EMT promoted migration, invasion, tumorigenesis, stemness, and metastasis of lung cancer cells in a TGF-β-independent fashion. Additionally, TGF-β1 promoted EMT progression synergistically with αvβ3 integrin, while a TGF-β signaling inhibitor showed no effect on αvβ3 integrin-induced partial EMT. Meanwhile, the microRNA-200 family abolished the αvβ3 integrin-induced partial EMT by suppressing αvβ3 integrin cell surface expression. These findings indicate that αvβ3 integrin is a key inducer of partial EMT, and highlight a new mechanism for cancer progression.
Highlights
Epithelial–mesenchymal transition (EMT) plays a pivotal role for tumor progression
To investigate the mechanisms by which the miR-200 family reverses αvβ[3] integrin-induced partial EMT, we examined the expression of αvβ[3] integrin
We found an unexpected result, where overexpression of αvβ[3] integrin in lung cancer cells induced partial EMT in a transforming growth factor-β (TGF-β)-independent fashion. β3 integrin was significantly increased in lung adenocarcinoma tumor tissues compared to normal lung tissues
Summary
Epithelial–mesenchymal transition (EMT) plays a pivotal role for tumor progression. Recent studies have revealed the existence of distinct intermediate states in EMT (partial EMT); the mechanisms underlying partial EMT are not fully understood. To investigate the functions of αvβ[3] integrin-induced partial EMT in lung cancer progression, we first conducted transwell cell migration and Matrigel invasion assays to assess the functions of αvβ[3] integrin in cell motility and invasiveness. We examined the effect of αvβ[3] integrininduced partial EMT in lung cancer cells on tumor development
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