Purpose: Investigate the role of regulator of chromosome condensation 2 (RCC2) on lung adenocarcinoma (LUAD) metastasis. Experimental Design: Clinical specimens were used to assess the impact of RCC2 on LUAD metastasis. Mouse models, cytobiology, and molecular biology assays were performed to elucidate the function and underlying mechanisms of RCC2 in LUAD. Results: RCC2 expression was frequently increased in LUADs (88/122, 72.13%). It was confirmed by analysis of a larger cohort of TCGA RNA-seq data containing 488 LUADs and 58 normal lung tissues (P < 0.001). Importantly, increased level of RCC2 was significantly associated with T status of tumor (P = 0.002), lymph node metastasis (P = 0.004), and advanced clinical stage (P = 0.001). Patients with LUAD with higher expression of RCC2 had shorter overall survival. Cox regression analysis demonstrated that RCC2 was an independent poorer prognostic factor for patients with LUAD. Moreover, forced expression of RCC2 promoted intrapulmonary metastasis in vivo and significantly enhanced LUAD cell migration, invasion, and proliferation in vitro. Further study found that RCC2 induced epithelial–mesenchymal transition (EMT) and also stimulated the expression of MMP-2 and MMP-9. In addition, RCC2 was able to activate JNK, while inhibition of JNK suppressed the effect of RCC2 on LUAD cell migration, invasion, EMT, and the expression of MMP-2 and MMP-9. Conclusions: RCC2 plays a pivotal role in LUAD metastasis by inducing EMT via activation of MAPK–JNK signaling. Clin Cancer Res; 23(18); 5598–610. ©2017 AACR.

TRIB1 promotes colorectal cancer cell migration and invasion through activation MMP-2 via FAK/Src and ERK pathways TRIB1 promotes colorectal cancer cell migration and invasion through activation MMP-2 via FAK/Src and ERK pathways

Double minute chromosomes (DMs) have important implications for cancer progression because oncogenes frequently amplified on them. We previously detected a functionally undefined gene amplified on DMs, Ribosomal L22-like1 (RPL22L1). The relationship between RPL22L1 and cancer progression is unknown. Here, RPL22L1 was characterized for its role in ovarian cancer (OC) metastasis and its underlying mechanism was examined. DNA copy number and mRNA expression of RPL22L1 in OC cells was analyzed using data obtained from The Cancer Genome Atlas and the Gene Expression Omnibus database. An immunohistochemical analysis of clinical OC specimens was performed and the relationships between expression level and clinicopathological factors were evaluated. Additionally, in vivo and in vitro assays were performed to understand the role of RPL22L1 in OC. RPL22L1 expression was higher in OC specimens than in normal tissues, and its expression level was highly positively correlated with invasion and lymph node metastasis (P < 0.05). RPL22L1 over-expression significantly enhanced intraperitoneal xenograft tumor development in nude mice and promoted invasion and migration in vitro. Additionally, RPL22L1 knockdown remarkably inhibited UACC-1598 cells invasion and migration. Further, RPL22L1 over-expression up-regulated the mesenchymal markers vimentin, fibronectin, and α-SMA, reduced expression of the epithelial markers E-cadherin, α-catenin, and β-catenin. RPL22L1 inhibition reduced expression of vimentin and N-cadherin. These results suggest that RPL22L1 induces epithelial-to-mesenchymal transition (EMT). Our data showed that the DMs amplified gene RPL22L1 is critical in maintaining the aggressive phenotype of OC and in triggering cell metastasis by inducing EMT. It could be employed as a novel prognostic marker and/or effective therapeutic target for OC.

COX-2 expression in ovarian cancer: an updated meta-analysis COX-2 expression in ovarian cancer: an updated meta-analysis

Introduction: Since the first fusion gene was discovered decades ago, a considerable number of fusion genes have been detected in leukemia. The majority of them are generated through chromosomal rearrangement or abnormal transcription. With the development of techniques, highthroughput sequencing method makes it possible to detect fusion genes systematically in multiple human cancers. Owing to their biological significance and tumor-specific expression, some of the fusion genes are attractive diagnostic tools and therapeutic targets. Tyrosine kinase inhibitors (TKI) targeting BCR-ABL1 fusions have been widely used to treat CML. The combination of ATRA and ATO targeting PML-RARA fusions has proven to be effective in acute promyelocytic leukemia (APL). Moreover, therapy with high dose cytarabine (HDAC) has significantly improved the prognosis of core binding factor (CBF) acute myeloid leukemia (AML) patients. Therefore, studies on fusion genes may benefit patients with leukemia by providing more diagnostic markers and therapies in the future. Conclusion: The presented review focuses on the history of fusion genes, mechanisms of formation, and treatments against specific fusion genes in leukemia.