The forkhead box M1 (FOXM1) transcription factor is one of the key genes inducing tumor invasion and metastasis by an unknown mechanism. In this study, we set out to investigate the effects of FOXM1 overexpression on metastatic human lung adenocarcinoma and the underlying mechanism. FOXM1 expression was analyzed in 78 frozen lung adenocarcinoma tissue samples using an Affymetrix microarray and a 155-paraffin-embedded lung adenocarcinoma tissue microarray with immunohistochemical detection. FOXM1 was found to be overexpressed in lung adenocarcinoma, particularly in metastatic patients, compared to non-metastatic patients. Knockdown of FOXM1 by a specific siRNA significantly suppressed EMT progression, migration and invasion of lung adenocarcinoma cells in vitro, and tumor growth and metastasis in vivo, whereas restored expression of FOXM1 had the opposite effect. FOXM1 binds directly to the SNAIL promoter through two specific binding sites and constitutively transactivates it. Collectively, our findings indicate that FOXM1 may play an important role in advancing lung adenocarcinoma progression. Aberrant FOXM1 expression directly and constitutively activates SNAIL, thereby promoting lung adenocarcinoma metastasis. Inhibition of FOXM1-SNAIL signaling may present an ideal target for future treatment.

Pancreatic cancer is among the deadliest malignancies; however, the genetic events that lead to pancreatic carcinogenesis in adults remain unclear. In vivo models in which these genetic alterations occur in adult animals may more accurately reflect the features of human cancer. In this study, we demonstrate that inactivation of Cdkn2b (p15ink4b) is necessary for induction of pancreatic cancer by oncogenic KRASG12D expression and inactivation of Tp53 and Cdkn2a in adult mouse pancreatic ductal cells (P60 or older). KRASG12D overexpression in these cells activated transforming growth factor-β signaling and expression of CDKN2B, which, along with CDKN2A, led to cellular senescence and protected cells from KRAS-mediated transformation via inhibition of retinoblastoma phosphorylation. These results show a critical role of CDKN2B inactivation in pancreatic carcinogenesis, and provide a useful adult animal model by genetic engineering via lentiviral delivery.

This study investigated the correlation of preoperative plasma fibrinogen level with distant metastasis and prognosis in esophageal squamous cell carcinoma (ESCC). A total of 255 patients with ESCC who underwent surgery in Zhejiang cancer hospital (Hangzhou, China), between October 2006 and December 2009, were evaluated in this retrospective study. Population controls were selected from a pool of cancer-free subjects in the same region. Each patient and cancer-free people provided 3-mL pretreatment blood. Plasma fibrinogen level was measured by the Clauss method. The effects of hyperfibrinogenemia on locoregional relapse-free survival (LRFS), distant metastasis-free survival (DMFS), relapse-free survival (RFS), and overall survival (OS) were assessed using Kaplan-Meier analysis. Independent prognostic factors were identified in the multivariate Cox analysis. The proportion of hyperfibrinogenemia was higher in ESCC patients than those in controls (40.4% vs 13.6%). Subjects with hyperfibrinogenemia had a significantly higher risk of ESCC than those with normal plasma fibrinogen level (adjust OR = 4.61; 95% CI = 3.02–7.01, P < 0.001) after adjusted for age, sex and smoking status. The Kaplan-Meier curves showed that patients with hyperfibrinogenemia had worse DMFS, RFS and OS (P < 0.001). Tumor length, lymph node metastasis and plasma fibrinogen level were independent prognostic factors of ESCC (P < 0.05). Increased plasma fibrinogen level was significantly associated with elevated risk of ESCC. Preoperative plasma fibrinogen level was a predictor of distant metastasis and independently associated with prognosis of patients with ESCC.