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Metastasis accounts for the high mortality rate associated with colorectal cancer (CRC), but metastasis regulators are not fully understood. To identify a novel gene involved in tumor metastasis, we used oligonucleotide microarrays, transcriptome distance analyses, and machine learning algorithms to determine links between primary and metastatic colorectal cancers. Aminopeptidase A (APA; also known as ENPEP) was selected as our focus because its relationship with colorectal cancer requires clarification. Higher APA mRNA levels were observed in patients in advanced stages of cancer, suggesting a correlation between ENPEP and degree of malignancy. Our data also indicate that APA overexpression in CRC cells induced cell migration, invasion, anchorage-independent capability, and mesenchyme-like characteristics (e.g., EMT markers). We also observed TWIST induction in APA-overexpressing SW480 cells and TWIST down-regulation in HT29 cells knocked down with APA. Both APA silencing and impaired APA activity were found to reduce migratory capacity, cancer anchorage, stemness properties, and drug resistance in vitro and in vivo. We therefore suggest that APA enzymatic activity affects tumor initiation and cancer malignancy in a TWIST-dependent manner. Results from RT-qPCR and the immunohistochemical staining of specimens taken from CRC patients indicate a significant correlation between APA and TWIST. According to data from SurvExpress analyses of TWIST1 and APA mRNA expression profiles, high APA and TWIST expression are positively correlated with poor CRC prognosis. APA may act as a prognostic factor and/or therapeutic target for CRC metastasis and recurrence. www.impactjournals.com/oncotarget/

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This study proposes a new and effective way to gain a better understanding of the features of the S-OIV genome and evolutionary processes based on the codon usage pattern. It is useful to trace influenza viral origins and cross-species virus transmission.

Taken the pore structure effects into account, a mathematical model to describe the interaction of mass transfers, the chemical reaction and the pore structure in the gas sensitive porous medium is presented and solved. The properties of the mass transfers and the reaction characteristics of the gas-sensitive porous system are analyzed. The effects of pore size distribution and porosity on the concentration field of detected gas and the effective utilization degree of the porous matrix are provided. The results indicate that the Thiele number, which can reflect the relative magnitude of chemical reaction rate and gas diffusion velocity in nature, is the main basis for judging the effects of various parameters. It usefully reproduces the observed effects of pore structure and reaction temperature on diffusion and chemical reaction response, showing that the gas sensitivity and the effective utilization coefficient of the gas sensitive porous medium can be controlled by adjusting key parameters.