IGHG1 promotes motility likely through epithelial-mesenchymal transition in ovarian cancer.

OBJECTIVE: Ovarian cancer (OC) is one of the leading causes of death for female cancer patients. COC166-9 is an OC-specific monoclonal antibody and we have identified immunoglobulin γ-1 heavy chain constant region (IGHG1) as its antigen. We explore the function of IGHG1 in proliferation, apoptosis and motility of OC cells further in this research. METHODS: IGHG1 expression in OC specimens was detected through immunohistochemistry. Real-time quantitative polymerase chain reaction (RT-qPCR) or western blotting assay was used to test IGHG1 expression in OC cells. Viability of OC cells was tested by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Flow cytometry or western blotting assay was used to detect cell cycle and apoptosis. Cellular motility was analyzed by using transwell assay and the markers of epithelial-mesenchymal transition (EMT) were tested through immunoblots. RESULTS: Although it exerts negligible effect on the viability and apoptosis of OC cells, IGHG1 could promote migration and invasion of malignant cells in vitro. Mechanistically, IGHG1 increases the expression of N-cadherin and Vimentin while decreases E-cadherin expression. Additionally, IGHG1 expression in OC specimens is higher relative to the paired normal counterparts. Further analysis demonstrates that the increased IGHG1 expression correlates positively with the lymph node metastasis of OC. CONCLUSIONS: IGHG1 promotes the motility of OC cells likely through executing the EMT program. Increased IGHG1 expression in OC specimens is associated with the lymph node metastasis.

Mesenchymal Stem Cells Promote Hepatocarcinogenesis via lncRNA-MUF Interaction with ANXA2 and miR-34a.

Accumulating evidence suggests that cancer-associated mesenchymal stem cells (MSC) contribute to the development and metastasis of hepatocellular carcinoma (HCC). Aberrant expression of long noncoding RNAs (lncRNA) has been associated with these processes but cellular mechanisms are obscure. In this study, we report that HCC-associated mesenchymal stem cells (HCC-MSC) promote epithelial-mesenchymal transition (EMT) and liver tumorigenesis. We identified a novel lncRNA that we termed lncRNA-MUF (MSC-upregulated factor) that is highly expressed in HCC tissues and correlated with poor prognosis. Depleting lncRNA-MUF in HCC cells repressed EMT and inhibited their tumorigenic potential. Conversely, lncRNA-MUF overexpression accelerated EMT and malignant capacity. Mechanistic investigations showed that lncRNA-MUF bound Annexin A2 (ANXA2) and activated Wnt/ß-catenin signaling and EMT. Furthermore, lncRNA-MUF acted as a competing endogenous RNA for miR-34a, leading to Snail1 upregulation and EMT activation. Collectively, our findings establish a lncRNA-mediated process in MSC that facilitates hepatocarcinogenesis, with potential implications for therapeutic targeting. Cancer Res; 77(23); 6704-16. ©2017 AACR.

Overexpression of S100A14 in human serous ovarian carcinoma.

S100 calcium binding protein A14 (S100A14) is a member of the S100 protein family that plays an important role in the progression of several types of cancer. In the present study, the expression and clinical effect of S100A14 was evaluated in serous ovarian carcinoma (SOC). SOC tissue specimens and a panel of normal ovarian and fallopian tubal tissue specimens were obtained between November 2008 and August 2012 from the Affiliated Hospital of Qingdao University. Immunohistochemistry (IHC) was used to detect the expression of S100A14 in the SOC and normal control tissues. In addition, ELISA was performed to assess S100A14 expression in a subset of serum samples. The association between the expression of S100A14 in SOC and the corresponding clinical and pathological data was analyzed. The IHC results revealed that S100A14 was mainly located in the cytoplasm of the majority of SOC cells, and the expression levels of S100A14 in the tumor tissues were significantly increased compared with the levels identified in normal ovarian specimens (P<0.001). Consistently, the serum levels of S100A14 in patients with SOC were also increased compared with the levels in healthy individuals (P<0.001). S100A14 expression was similar in the epithelium of SOC lesions and the fallopian tube, which supported the dualistic model for ovarian serous carcinogenesis. Additional analysis of the expression of S100A14 and corresponding clinical and pathological data revealed the correlation between the elevated expression of S100A14 and resistance to platinum-based chemotherapy. However, the protein level of S100A14 was not associated with the pathological stage, differentiation or metastasis of SOC. Overall, the present results demonstrate that S100A14 is likely to be involved in the resistance of SOC to platinum-based chemotherapy.

High expression of S100P is associated with unfavorable prognosis and tumor progression in patients with epithelial ovarian cancer.

Accumulating evidence has demonstrated that S100P is involved in the tumorigenesis and progression of multiple cancers. In the current study, we evaluated the expression of S100P in epithelial ovarian cancer and assessed its relevance to clinicopathological characteristics. Moreover, we investigated the biological effects of S100P using A2780 and SKOV3 cells. S100P expression was significantly increased in epithelial ovarian cancer specimens compared with fallopian tube tissues and normal ovary tissues. And high expression of S100P in epithelial ovarian cancer samples was significantly associated with tumor stage (P<0.001), serum CA125 level (P=0.026), residual tumor (P<0.001), ascites (P<0.001) and lymph nodes metastasis (P<0.001). Multivariate Cox analysis showed that S100P expression was an independent prognostic factor of overall survival (OS) and progression free survival (PFS) (P=0.017 and 0.031, respectively). Functional assays showed that overexpression of S100P promoted cell proliferation and cell cycle progression but did not affect cell migration and invasion in A2780 and SKOV3 cells. These data suggest that S100P may contribute to tumor development in epithelial ovarian cancer and could be a useful marker for the prognosis of epithelial ovarian cancer patients.

S100A14, a mediator of epithelial-mesenchymal transition, regulates proliferation, migration and invasion of human cervical cancer cells.

S100A14 is an EF-hand calcium-binding protein that has been reported to exert its biological effects on different types of cells. However, the potential clinical significance and biological functions of S100A14 in cervical cancer has not yet been clarified. In this study, we firstly examined the correlation between S100A14 expression and clinical-pathological parameters in cervical cancers. Next, we observed the effect of S100A14 on cell cycle progression, cell proliferation, migration and invasion by employing lentiviral-mediated overexpression and knockdown of S100A14 in cervical cancer cells. Furthermore, we investigated the underlying mechanism of S100A14 affecting cell migration and invasion. Immunohistochemistry analysis demonstrated that S100A14 expression was associated with the International Federation of Gynecology and Obstetrics (FIGO) stage (P = 0.025) and lymph node (LN) metastasis (P = 0.001). Functional assays showed that S100A14 overexpression increased the proportion of G2/M phase, promoted cell proliferation, migration, and invasion, whereas S100A14 knockdown exhibited adverse effect on above properties. Mechanistic investigation demonstrated that S100A14 can act as a mediator of epithelial-mesenchymal transition (EMT). And overexpression of S100A14 increased expression of N-cadherin and Vimentin while decreased expression of E-cadherin. The opposite results were observed in S100A14-silenced cells. Taken together, our data indicate that S100A14 has a crucial role in cervical cancer progression. This study significantly increases our understanding of S100A14 functional roles in cervical cancer, which may lead to the development of a novel therapeutic target for cervical cancer.