TRIM14 promotes colorectal cancer cell migration and invasion through the SPHK1/STAT3 pathway

Abstract Background Colorectal cancer (CRC) is one of the most lethal malignancies. Tripartite Motif Containing 14 (TRIM14) is a member of TRIM family proteins, which are involved in the pathogenesis of various cancers. This study aimed to investigate TRIM14 expression in CRC tissues, and its effects on the migration and invasion of CRC cell lines. Methods TRIM14 mRNA expression was detected by real-time PCR analysis. Cell migration and invasion were measured by Transwell assays. Protein expression was assessed by western blot analysis. Results The expression of TRIM14 was significantly higher in CRC tissues than in matched non-cancerous tissues. TRIM14 knockdown by specific short hairpin RNA (shRNA) attenuated CRC cell migration and invasion, whereas TRIM14 overexpression caused reverse effect. Moreover, TRIM14 positively regulated the protein levels of sphingosine kinase 1 (SPHK1) and phosphorylated STAT3 (p-STAT3), as well as the mRNA and protein expression of matrix metalloproteinase 2, MMP9 and vascular endothelial growth factor, which are transcriptional targets of the STAT3 signaling pathway. Importantly, the blockage of the SPHK1/STAT3 signaling pathway by SKI-II or AG490 could reverse the TRIM14-promoted CRC cell migration and invasion. Conclusions Our results reveal a critical role for TRIM14 in promoting migration and invasion of CRC cells, and suggest TRIM14 may serve as a potential molecular target to prevent CRC metastasis

A Cretaceous pole from south China, and the Mesozoic hairpin turn of the Eurasian apparent polar wander path

International audienceTo contribute to the apparent polar wander path (APWP) of the South China Block and Eurasia in general, we collected paleomagnetic samples from Mesozoic red beds around the city of Ya' an (30°N, 103°E) in the western tip of the Sichuan Basin. In this paper we present the results from 373 oriented cores taken from one section representing 3 km of sedimentary rocks. The section is dated with continental ostracods and with a magnetostratigraphic correlation between a densely sampled 272-m sequence and the polarity time scale, giving an upper Jurassic to Upper Cretaceous or Lower Tertiary age. The remanent direction is remarkably stable throughout the section (D=2.0°, I=34.2°, k=63.1,α95=3.6°, N=26/28 sites). While this fact might suggest that the section has been remagnetized, paleomagnetic and rock magnetic tests indicate that the remanence is primary. The pole position (78.6°N, 273.4°E, dp=2.4°, dm=4.1°) corresponds to a rather low paleolatitude (λ=18.8°±2.4°) but is consistent with other Cretaceous poles from China. If one accepts the Eurasian APWP of Irving and Irving (1982), this result would imply that more than 1000 km of shortening took place between South China and Eurasia, following the acquisition of the remanence. However, there is no geological evidence for this large shortening. We propose that the remanence was acquired within the time corresponding to the tip of the hairpin turn (∼150–50 Ma) in the revised APWP of Besse and Courtillot (this issue). The local geology suggests that the syncline from which the samples were taken has been rotated by 15°±5° counterclockwise, which is reflected in a similar discrepancy between the measured paleodeclination and that predicted by the Besse and Courtillot (this issue) Eurasian APWP. After correcting for this rotation, the pole position is 70.9°N, 225.2°E (dp=2.4°, dm=6.5°). We conclude that Eurasia was fully assembled by the end of the Jurassic and that the Mesozoic Eurasian hairpin turn is a real feature

Bioprocess development for the production of mouse-human chimeric anti-epidermal growth factor receptor vIII antibody C12 by suspension culture of recombinant Chinese hamster ovary cells

The mouse-human chimeric anti-epidermal growth factor receptor vIII (EGFRvIII) antibody C12 is a promising candidate for the diagnosis of hepatocellular carcinoma (HCC). In this study, 3 processes were successfully developed to produce C12 by cultivation of recombinant Chinese hamster ovary (CHO-DG44) cells in serum-free medium. The effect of inoculum density was evaluated in batch cultures of shaker flasks to obtain the optimal inoculum density of 5 × 105 cells/mL. Then, the basic metabolic characteristics of CHO-C12 cells were studied in stirred bioreactor batch cultures. The results showed that the limiting concentrations of glucose and glutamine were 6 and 1 mM, respectively. The culture process consumed significant amounts of aspartate, glutamate, asparagine, serine, isoleucine, leucine, and lysine. Aspartate, glutamate, asparagine, and serine were particularly exhausted in the early growth stage, thus limiting cell growth and antibody synthesis. Based on these findings, fed-batch and perfusion processes in the bioreactor were successfully developed with a balanced amino acid feed strategy. Fed-batch and especially perfusion culture effectively maintained high cell viability to prolong the culture process. Furthermore, perfusion cultures maximized the efficiency of nutrient utilization; the mean yield coefficient of antibody to consumed glucose was 44.72 mg/g and the mean yield coefficient of glutamine to antibody was 721.40 mg/g. Finally, in small-scale bioreactor culture, the highest total amount of C12 antibody (1,854 mg) was realized in perfusion cultures. Therefore, perfusion culture appears to be the optimal process for small-scale production of C12 antibody by rCHO-C12 cells