Deeper mechanistic understanding of non-small cell lung cancer (NSCLC), a leading cause of total cancer-related deaths, may facilitate the establishment of more effective therapeutic strategies. In this study, pituitary tumor transforming gene ( PTTG1 ) expression was associated with lymph node and distant metastasis in patients with NSCLC and was correlated with patient survival. Reduction of PTTG1 by small interfering RNA (siRNA) inhibits the migration and invasion of NSCLC cells by mediating matrix metalloproteinases expression. To the best of our knowledge, this study is the first to report that PTTG1 promotes epidermal growth factor (EGF) induced the phosphorylation of LIN-11, Isl1 and MEC-3 protein domain kinase and cofilin, a critical step in cofilin recycling and actin polymerization. Additionally, EGF-induced Akt phosphorylation was suppressed through knockdown of PTTG1. Interestingly, miR-186 can modulate PTTG1 protein expression. As observed from the animal experiment in this study, knockdown of PTTG1 through siRNA and overexpression of miR-186 inhibited invasive activity of NSCLC cells toward the SCID mice lung. In summary, our in vitro and in vivo results indicate that PTTG1 modulated by miR-186 has an important function in NSCLC invasion/metastasis. This study identified both PTTG1 and miR-186 as potential anti-invasion targets for therapeutic intervention in NSCLC.

Lung cancer is a leading cause of cancer-related mortality worldwide and non-small-cell lung carcinoma (NSCLC) is responsible for almost 80% of lung cancer-related deaths. Identifying novel molecules that can repress the invasiveness and metastasis of lung cancer will facilitate the development of new antilung cancer strategies. The aim of this study is to determine the roles of NUAK1 (a downstream of Akt) and miR-204 in the invasiveness and metastasis of NSCLC and to reveal the correlation between NUAK1 and miR-204. The expression of NUAK1 in primary human NSCLC tissues was evaluated by immunohistochemistry. Real-time PCR was employed to measure the expression level of miR-204. The effect of NUAK1 and miR204 on the prognosis of NSCLC patients was evaluated by log-rank test. The siRNA transfection was used to manipulate the expression levels of NUAK1 and miR204 in cancer cells. Chemotaxis assay, Scratch assay, and Matrigel invasion assay were performed to evaluate the migration and invasion of cells. Cellular F-actin measurement was used to measure F-actin polymerisation in lung cancer cells. Western blot was used to detect the expression levels of corresponding proteins. The Luciferase assay and RNA immunoprecipitation were used to confirm the actual binding site of miR-204 to 3′UTR of NUAK1. Increased expression of NUAK1 is correlated with the invasiveness and metastasis of human NSCLC. Knockdown of NUAK1 inhibited cell migration and invasion. In addition, this study showed that NUAK1 influenced mTOR phosphorylation and induced the phosphorylation of p70S6K1 and eukaryotic initiation factor 4E-binding protein1 (4E-BP1), two downstream targets of mTOR in NSCLC cells. At the same time, decreased expression of miR-204 promoted NSCLC progression and, contrarily, manipulated upregulation of miR-204-inhibited cell migration and invasion. There is clinical relevance between miR-204 downregulation and NUAK1 upregulation in human NSCLC. Furthermore, we found that miR-204 inhibited NSCLC tumour invasion by directly targeting and downregulating NUAK1 expression. Finally, our data suggested that the downregulation of miR-204 was due to hypermethylation of its promoter region. Our results indicate that NUAK1 is excessively expressed in NSCLC and plays important roles in NSCLC invasion. The miR-204 acts as a tumour suppressor by inhibiting NUAK1 expression in NSCLC. Both NUAK1 and miR-204 may serve as potential targets of NSCLC therapy.

Studies have shown that cancer-associated fibroblasts (CAFs) play an irreplaceable role in the occurrence and development of tumors. Therefore, exploring the action and mechanism of CAFs on tumor cells is particularly important. In this study, we compared the effects of CAFs-derived exosomes and normal fibroblasts (NFs)-derived exosomes on breast cancer cells migration and invasion. The results showed that exosomes from both CAFs and NFs could enter into breast cancer cells and CAFs-derived exosomes had a more enhancing effect on breast cancer cells migration and invasion than NFs-derived exosomes. Furthermore, microRNA (miR)-18b was upregulated in CAFs-derived exosomes, and CAFs-derived exosomes miR-18b can promote breast cancer cell migration and metastasis by specifically binding to the 3′UTR of Transcription Elongation Factor A Like 7 (TCEAL7). The miR-18b-TCEAL7 pathway promotes nuclear Snail ectopic activation by activating nuclear factor-kappa B (NF-κB), thereby inducing epithelial-mesenchymal transition (EMT) and promoting cell invasion and metastasis. Moreover, CAFs-derived exosomes miR-18b could promote mouse xenograft model tumor metastasis. Overall, our findings suggest that CAFs-derived exosomes miR-18b promote nuclear Snail ectopic by targeting TCEAL7 to activate the NF-κB pathway, thereby inducing EMT, invasion, and metastasis of breast cancer. Targeting CAFs-derived exosome miR-18b may be a potential treatment option to overcome breast cancer progression.

Glioma is the most common form of primary malignant brain cancers. Tumor cell invasiveness is a critical challenge in the clinical management of glioma patients. The invasive biological feature of glioma cell is stimulated by both autocrine and paracrine factors including chemokine IL-8. In this study, we report that the production of IL-8 is higher in glioma tissues and cells than adjacent nontumor tissues (ANT) and normal glial cells. Autocrine IL-8 can increase the invasive ability of glioma cells by binding to CXCR1. In addition, high expression of IL-8 indicates poor prognosis of glioma patients. Furthermore, IL-8 is capable of modulating cell migration and invasion by regulating the activation of RAC1 which resulted in cytoskeletal reorganisation in an ELMO1 dependent manner. Finally, we found that IL-8 could enhance mesenchymal transition(MT) of glioma cells by activating ELMO1-NF-κB-Snail signaling. Our data indicate that IL-8 autocrine is responsible for the invasive phenotype of glioma and IL-8 may be a useful prognostic marker for glioma and novel therapeutic target for glioma invasion intervention.