Migration Of Human Lung Adenocarcinoma Cells Research Articles

AK2 Promotes the Migration and Invasion of Lung Adenocarcinoma by Activating TGF-β/Smad Pathway In vitro and In vivo.

Adenylate kinase 2 (AK2) is a wide-spread and highly conserved protein kinase whose main function is to catalyze the exchange of nucleotide phosphate groups. In this study, we showed that AK2 regulated tumor cell metastasis in lung adenocarcinoma. Positive expression of AK2 is related to lung adenocarcinoma progression and poor survival of patients. Knockdown or knockout of AK2 inhibited, while overexpression of AK2 promoted, human lung adenocarcinoma cell migration and invasion ability. Differential proteomics results showed that AK2 might be closely related to epithelial-mesenchymal transition (EMT). Further research indicated that AK2 regulated EMT occurrence through the Smad-dependent classical signaling pathways as measured by western blot and qPCR assays. Additionally, in vivo experiments showed that AK2-knockout in human lung tumor cells reduced their EMT-like features and formed fewer metastatic nodules both in liver and in lung tissues. In conclusion, we uncover a cancer metastasis-promoting role for AK2 and provide a rationale for targeting AK2 as a potential therapeutic approach for lung cancer.

Shikonin blocks human lung adenocarcinoma cell migration and invasion in the inflammatory microenvironment via the IL‑6/STAT3 signaling pathway.

Increasing evidence indicates that the inflammatory tumor microenvironment can lead to cancer cell metastasis. Shikonin, which is extracted from the Chinese herb Zicao (the dried root of Lithospermum erythrorhizon), possesses various pharmacological effects, but its effect on tumor metastasis in the inflammatory microenvironment remains unknown. In the present study, we aimed to investigate the potential effect of shikonin on tumor metastasis in an inflammatory microenvironment as well as the underlying molecular mechanisms. It was found that, in the inflammatory microenvironment simulated by THP-1 cell conditioned medium (THP-1-CM) in vitro, shikonin significantly inhibited the epithelial-mesenchymal transition (EMT), migration and invasion of human lung adenocarcinoma cell lines A549 and H1299. In addition, we found that interleukin-6 (IL-6), which is expressed in THP-1-CM, promoted the EMT of lung adenocarcinoma cells, and shikonin markedly inhibited IL-6-induced EMT and cell motility. Moreover, shikonin inhibited IL-6-induced phosphorylation of signal transducer and activator of transcription 3 (STAT3), prevented phosphorylated STAT3 (p-STAT3) translocation into the nucleus, and suppressed p-STAT3 transactivation activity. Additionally, it was found that shikonin inhibited lung metastasis, EMT and expression of p-STAT3 of A549 cells in vivo. Furthermore, IL-6 levels in human lung adenocarcinoma tissues were significantly associated with tumor-node-metastasis stage and lymph node metastasis, and its expression was correlated with tumor-associated macrophage (TAM) infiltration. Together, these results suggest that shikonin suppresses the migration and invasion of human lung adenocarcinoma cells in an inflammatory microenvironment involving the IL-6/STAT3 signaling pathway.

MiR-218 suppresses epithelial-to-mesenchymal transition by targeting Robo1 and Ecop in lung adenocarcinoma cells.

Although, miR-218 has been implicated in epithelial-to-mesenchymal transition process, the detailed mechanisms of miR-218 involvement in epithelial-to-mesenchymal transition in human lung adenocarcinoma cell are still unclear. miR-218 function assays and its target gene analysis were performed. miR-218 suppresses human lung adenocarcinoma cell migration and invasion and inhibits its target gene, Ecop and Robo1 expression, which subsequently suppresses NF-κB activity and its downstream targets. miR-218 inhibits human lung adenocarcinoma cell migration and invasion via the suppression of Ecop and Robo1 expression, thus suggesting that miR-218 could serve as a potential therapeutic target.

Abstract 77: Study of the effect of MAPRE2 on human lung adenocarcinoma cell migration and invasion

Abstract Lung cancer is the most malignant disease which makes lots of people dead worldwide. More and more evidences showed that cancers might arise from chromosome alteration, including amplification or deletion. Our previous study integrating microarray-based comparative genomic hybridization and affymetrix gene expression profiles identified a potential candidate gene, MAPRE2, in a lung cancer cell line model with different invasion capability. MAPRE2 (Microtubule-associated protein RP/EB family member 2) is usually located on microtubule and interactes with tumor suppress gene APC (adenomatous polyposis coli). MAPRE2 might be involved in microtubule polymerization, cell migration and tumorigenesis of colorectal cancers, but its function is unclear. The purpose of this study is to investigate the effects of MAPRE2 on cancer cell function. The results of real-time PCR and western blotting showed that DNA copy number, RNA and protein level of MAPRE2 were higher in low invasive lung cancer cells than in highly invasive cells. Immunofluorescence assay indicated that the distribution of MAPRE2 protein was predominant in cytoplasm. Furthermore, overexpression of MAPRE2 could inhibit cancer cell proliferation, anchorage- dependent and -independent growth, cell motility, invasion ability in vitro and tumor growth and metastasis in vivo. On the contrary, silencing MAPRE2 enhanced lung cancer cell proliferation and invasion ability. Consider the whole map of MAPRE2-regulated signalling, transcriptomic analysis was performed and the results showed that MAPRE2 could affect 1039 genes (ANOVA, FDR< 0.05) which are dominantly involved in cell cycle and adhesion-related biological signalling, such as MAPK, focal adhesion and tight junction pathways. Our results suggested that MAPRE2 might play a significant role in MAPRE2-mediated pathways to suppress tumorigenesis and metastasis. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 77. doi:1538-7445.AM2012-77

Abstract 2188: Effect of the protein complex formation of a novel tumor suppressor HLJ1 and nuclear protein p54nrb on human lung adenocarcinoma cell migration and invasion

Abstract Lung cancer is the most common cause of cancer deaths in the world, and the incidence is increasing each year. In the previous studies, we have identified and characterized a novel tumor/invasion suppressor gene HLJ1 (human liver DnaJ-like protein, also called DNAJB4) in a lung cancer cell line model with different invasion capability. However, the suppressive mechanism of HLJ1 is unclear. Therefore, the objective of this study is to investigate and characterize the proteins interacting with HLJ1. To obtain the novel HLJ1-binding protein, the differentially cultured density of tumor cell is employed to mimic metastatic characteristics in vitro. We identified two proteins, p54nrb and PSF, that can interact with HLJ1 in high cell culture density by immunoprecipitation assay and MALDI-TOF analysis. The complex of HLJ1 and p54nrb was confirmed in vitro and in vivo by co-immunoprecipitation, GST pull-down and mammalian two-hybrid assay. In addition, the results of GST pull-down assay indicated that p54nrb can interact with HLJ1 through HTH motif. We also found that the expressions of both HLJ1 and p54nrb are increased in A549, CL1-0, CL1-5 and CL1-5F4 cancer cell lines while are culturing in high cell density. The results of immunofluorescent staining and cytosolic/nuclear protein fraction revealed that p54nrb is mainly located in the nucleus. Furthermore, we found that over-expression of p54nrb protein in the highly invasive lung cancer cell line, CL1-5, can reduce cancer cell proliferation, colony formation, invasion and migration. On the other hand, p54nrb was decreased when most cells are in DNA synthesis phase. Once over-expression of p54nrb in CL1-5 cell line, the cell cycle would arrest in G1 phase to reduce cancer cell proliferation. Investigating the action mechanism of HLJ1-p54nrb interaction is important, it may not only provide a new insight to understand the pathway of metastasis and growth regulation but also be as the new target molecule for anti-cancer therapy in the future. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 2188. doi:10.1158/1538-7445.AM2011-2188

Regulation of Human Lung Adenocarcinoma Cell Migration and Invasion by Macrophage Migration Inhibitory Factor

Macrophage migration inhibitory factor (MIF) is expressed and secreted in response to mitogens and integrin-dependent cell adhesion. Once released, autocrine MIF promotes the activation of RhoA GTPase leading to cell cycle progression in rodent fibroblasts. We now report that small interfering RNA-mediated knockdown of MIF and MIF small molecule antagonism results in a greater than 90% loss of both the migratory and invasive potential of human lung adenocarcinoma cells. Correlating with these phenotypes is a substantial reduction in steady state as well as serum-induced effector binding activity of the Rho GTPase family member, Rac1, in MIF-deficient cells. Conversely, MIF overexpression by adenovirus in human lung adenocarcinoma cells induces a dramatic enhancement of cell migration, and co-expression of a dominant interfering mutant of Rac1 (Rac1(N17)) completely abrogates this effect. Finally, our results indicate that MIF depletion results in defective partitioning of Rac1 to caveolin-containing membrane microdomains, raising the possibility that MIF promotes Rac1 activity and subsequent tumor cell motility through lipid raft stabilization.