As shown from our results, both PDBu and HGF treatment induced increased expression of N-WASP (Fig

As shown from our results, both PDBu and HGF treatment induced increased expression of N-WASP (Fig.?6a). is frequently overexpressed in cancer, but the exact mechanism of regulation is not yet fully understood. Methods The expression level of CTTN in human non-small cell lung cancer (NSCLC) tissues was detected by qRT-PCR. Cell migration, invasion and invadopodia formation were assessed in vitro by wound-healing, transwell assay and immunofluorescence, respectively. The dual-luciferase reporter assay was used to identify the direct target of miR-182. Results Hepatocyte growth factor (HGF) and phorbol 12,13-dibutyrate (PDBu) can induce CTTN expression, motility, and invasion ability, as well as invadopodia formation in non-small cell lung cancer (NSCLC). Moreover, miR-182 suppressed metastasis and invadopodia formation by targeting CTTN in NSCLC. Our qRT-PCR results showed that CTTN expression was inversely correlated with miR-182 expression that suppressed invadopodia formation via suppression of the Cdc42/N-WASP pathway. Furthermore, miR-182 negatively regulated invadopodia function, and suppressed extracellular matrix(ECM) degradation in lung cancer cells by inhibiting cortactin. Conclusion Collectively, Maraviroc (UK-427857) our results demonstrated that miR-182 targeted CTTN gene in NSCLC and suppressed lung cancer invadopodia formation, and thus suppressed lung cancer metastasis. This suggests a therapeutic application of miR-182 in NSCLC. Electronic supplementary material The online version of this article (10.1186/s13046-018-0824-1) contains supplementary material, which is available to authorized users. Keywords: Lung cancer, miRNA-182, Cortactin, Metastasis, Invadopodia Background As the most common cause of cancer-related death worldwide, lung cancer has been a growing problem in China since 2000 due to risk factors such as smoking, air pollution and an aging population [1, 2]. Despite the development of many treatment strategies, the long-term survival rate of lung cancer patients is still very low. The cause of death for the vast majority of cancer patients is the development of metastatic lesions at sites distant from that of the primary tumor. Metastasis is the leading cause of cancer mortality and is a major hurdle for lung cancer treatment. Metastasis occurs when tumor cells invade basement membranes and blood vessels to colonize other tissues. It is generally agreed that the process of tumor metastasis is a multi-step process and under precise regulation. However, the exact molecular mechanism of metastasis is not fully understood and the molecular pathways underlying each step are still obscure. Invasion of cells through layers of extracellular matrix (ECM) is a key step in tumor metastasis, Maraviroc (UK-427857) facilitated by invadopodia, which actin-rich protrusions of the plasma membrane that are associated with the degradation of the ECM in cancer invasiveness and metastasis [3]. By providing direct evidence of the functional importance of invadopodia in cancer cell extravasation, many Maraviroc (UK-427857) studies have demonstrated that invadopodia play a crucial role in the metastatic cascade and represent a potential therapeutic target for anti-metastasis strategies [4, 5]. Invadopodia adhesion sites in tumor cells are recognized by dot-like aggregates of actin and cortactin, and their membranes penetrate the matrix in the form of filopodia-like extensions assisted by membrane-associated proteolytic Cd86 enzymes. In general, invadopodia components fall into two classes of molecules: (1) proteins involved with actin polymerization and membrane remodeling and (2) ECM-degrading proteases. Emerging evidence has revealed a critical role for cortactin in invadopodia as well as in promoting cell motility and invasion [6C8]. Cortactin, plays an important role in actin assembly, scaffolding or cytoskeletal arrangement and membrane trafficking; Cortactin is also a universally important player in invadopodia function, and is likely to be a critical player in invadopodia-associated ECM degradation. As a result, cortactin is frequently used as an invadopodia marker. In addition, several studies have reported that cortactin is often overexpressed in tumors and is associated with metastasis and poor prognosis of patients [9C11]. Cortactin is a potential molecular driver in several cancers, including lung, brain, and colorectal cancer [12, 13]. miRNAs are endogenous and small non-coding RNAs of 20C25 nucleotides in length. They can regulate cell survival, proliferation, differentiation, migration, invasion and metastasis via binding to the 3 untranslated region (UTR) of some target genes [14]. It’s been reported that one-third of individual genes could be regulated by miRNAs [15] approximately. Increasing evidence provides indicated that miRNAs may work as either oncogenes or tumor suppressors in the malignant development of various malignancies, including lung cancers [14, 16, 17]. As you person in the miR-183/??96/??182 cluster, miR-182 has been proven to be engaged in individual cancer tumor procedures directly, such as for example tumorigenesis, metastasis and migration also to be a significant participant in regulating tumor development in a variety of tumors, including.

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