BackgroundThe elevated expression of vascular endothelial growth factor C (VEGF-C) is correlated with clinical cervical cancer metastasis and patient survival, which is interpreted by VEGF-C functions to stimulate angiogenesis and lymphatic genesis. However, the direct impact of VEGF-C on cervical cancer cell motility remains largely unknown.MethodsIn this study, we investigated the effects of VEGF-C on actin cytoskeleton remodeling and on cervical cancer cell migration and invasion and how the actin-regulatory protein, moesin regulated these effects through RhoA/ROCK-2 signaling pathway.ResultsOn cervical carcinoma cell line SiHa cells, exposure of VEGF-C triggered remodeling of the actin cytoskeleton and the formation of membrane ruffles, which was required for cell movement. VEGF-C significantly enhanced SiHa cells horizontal migration and three-dimensional invasion into matrices. These actions were dependent on increased expression and phosphorylation of the actin-regulatory protein moesin and specific moesin siRNA severely impaired VEGF-C stimulated-cell migration. The extracellular small GTPase RhoA/ROCK-2 cascade mediated the increased moesin expression and phosphorylation, which was discovered by the use of Y-27632, a specific inhibitor of Rho kinase and by transfected constitutively active, dominant-negative RhoA as well as ROCK-2 SiRNA. Furthermore, in the surgical cervical specimen from the patients with FIGO stage at cervical intra-epithelial neoplasia and I-II cervical squamous cell carcinoma, the expression levels of moesin were found to be significantly correlated with tumor malignancy and metastasis.ConclusionsThese results implied that VEGF-C promoted cervical cancer metastasis by upregulation and activation of moesin protein through RhoA/ROCK-2 pathway. Our findings offer new insight into the role of VEGF-C on cervical cancer progression and may provide potential targets for cervical cancer therapy.

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Estrogen promotes breast cancer metastasis. However, the detailed mechanism remains largely unknown. The actin binding protein ezrin is a key component in tumor metastasis and its over-expression is positively correlated to the poor outcome of breast cancer. In this study, we investigate the effects of 17β-estradiol (E2) on the activation of ezrin and its role in estrogen-dependent breast cancer cell movement. In T47-D breast cancer cells, E2 rapidly enhances ezrin phosphorylation at Thr567 in a time- and concentration-dependent manner. The signalling cascade implicated in this action involves estrogen receptor (ER) interaction with the non-receptor tyrosine kinase c-Src, which activates the phosphatidylinositol-3 kinase/Akt pathway and the small GTPase RhoA/Rho-associated kinase (ROCK-2) complex. E2 enhances the horizontal cell migration and invasion of T47-D breast cancer cells in three-dimensional matrices, which is reversed by transfection of cells with specific ezrin siRNAs. In conclusion, E2 promotes breast cancer cell movement and invasion by the activation of ezrin. These results provide novel insights into the effects of estrogen on breast cancer progression and highlight potential targets to treat endocrine-sensitive breast cancers.

SummaryIntramuscular fat (IMF) content is a critical factor affecting meat flavor, juiciness, tenderness, and color. Therefore, the improvement of IMF content is one of the hotspots of animal science research. Fat deposition is the result of a combination of increased number of fat cells and cellular hypertrophy. In addition, transcription factors can influence the number of adipocytes and regulate lipid metabolism. The progress of the transcription factors regulating adipocyte differentiation in beef cattle, including IMF cell sources, and promoting or inhibiting adipogenic differentiation of transcription factors is reviewed in this paper.

The buffalo (Bubalus bubalis L.) is prevalent in China and the increasing demand for meat production has changed its role from being a beast of burden to a meat source. The low fat deposition level has become one of the main barriers for its use in meat production. It is urgent to reveal factors involved in fat deposition in buffalo. This study performed RNA sequencing to investigate both long noncoding RNAs (lncRNAs) and mRNAs of adipose tissues in young and adult buffalos. A total of 124 lncRNAs and 2008 mRNAs showed differential expression patterns between young and adult samples. Coexpression analysis and functional enrichment revealed 585 mRNA–lncRNA pairs with potential function in fat deposition. After validation by qRT-PCR, we focused on a lncRNA transcribed from the ubiquinone oxidoreductase subunit C2 (NDUFC2) antisense (AS) strand which showed high correlation with thyroid hormone responsive protein (THRSP). NDUFC2-AS lncRNA is highly expressed in adipose tissue and maturation adipocytes and mainly exists in the nucleus. Functional assays demonstrated that NDUFC2-AS lncRNA promotes adipogenic differentiation by upregulating the expression levels of THRSP and CCAAT enhancer binding protein alpha (C/EBPα) in buffalo. These results indicate that NDUFC2-AS lncRNA promotes fat deposition in buffalo.