Silence of ezrin modifies migration and actin cytoskeleton rearrangements and enhances chemosensitivity of lung cancer cells in vitro

Abstract

Ezrin, primarily acts as a linker between the plasma membrane and the cytoskeleton, is involved in many cellular functions, including regulation of actin cytoskeleton, control of cell shape, adhesion, motility, and modulation of signaling pathways. Although ezrin is now recognized as a key component in tumor metastasis, its roles and the underlying mechanisms remain unclear. In the present study, we chose highly metastatic human lung carcinoma 95D cells, which highly express the ezrin proteins, as a model to examine the functional roles of ezrin in tumor suppression. An ezrin-silenced 95D cell line was established using lentivirus-mediated short hairpin RNA method. CCK-8 assay and soft agar assay analysis showed that downregulation of ezrin significantly suppressed the tumorigenicity and proliferation of 95D cells in vitro. cell migration and invasion studies showed that ezrin-specific deficiency in the cells caused the substantial reduction of the cell migration and invasion. In parallel, it also induced rearrangements of the actin cytoskeleton. Flow cytometry assay showed that changes in the ezrin protein level significantly affected the cell cycle distribution and eventual apoptosis. Furthermore, further studies showed that ezrin regulated the expression level of E-cadherin and CD44, which are key molecules involved in cell growth, migration, and invasion. Meanwhile, the suppression of ezrin expression also sensitized cells to antitumor drugs. Altogether, our results demonstrated that ezrin played an important role in the tumorigenicity and metastasis of lung cancer cells, which will benefit the development of therapeutic strategy for lung cancer.

Transcriptome Sequencing Reveals Key Pathways and Genes Associated with Cisplatin Resistance in Lung Adenocarcinoma A549 Cells

“…Previous studies of tumor metastasis suggested that strongly and weakly invasive cancer cells differ in terms of the reorganization of the actin cytoskeleton[37]. Chen et al found that knockdown of the expression of the actin cytoskeleton protein ezrin contributed to sensitizing lung cancer cells to cisplatin and pirarubicin[38]. …”

Ezrin Enhances EGFR Signaling and Modulates Erlotinib Sensitivity in Non–Small Cell Lung Cancer Cells

“…Expression levels of ezrin were found to be significantly higher in primary cancer tissues than matched normal lung tissues [23]. Suppression of ezrin expression in NSCLC cell lines leads to reduced migration and invasion, anchorage-independent growth ability, and increased drug sensitivity [24].…”

MicroRNAs in osteosarcoma

“…Its direct target is ezrin, an important member of the ezrin-radixin-moesin (ERM) family. Ezrin functions as a cross-linker between the actin cytoskeleton and the plasma membrane, and is intimately associated with cancers including chondrosarcoma, Ewing's sarcoma and lung cancer [42][43][44]. Studies from our own and other groups have demonstrated that overexpression of ezrin promotes invasion, migration and metastasis of OS cells [45], but ezrin silencing or its small molecule inhibitors NSC305787 and NSC668394 protect against OS development [46,47].…”