No abstract

Paternally expressed gene 10 (PEG10) has been identified as a genetic imprinted gene, which is important for apoptosis resistance in cancer cells. Mounting evidence suggests that PEG10 is expressed in the majority of hepatocellular carcinoma (HCC) cells with growth-promoting activity. In the present study, we evaluated the correlation between PEG10 expression and the clinicopathological features of lung, breast and HCC tumors, and predicted the relationship between survival and expression levels of PEG10 in lung cancer patients. Furthermore, we chose non-small cell lung cancer cell line A549 as a model to analyze the function of PEG10 in proliferation and metastasis in vitro. Our results revealed that expression of PEG10 was closely correlated with clinical TNM grade and patient prognosis in lung cancer. PEG10 enhanced cell proliferation and promoted tumor cell migration and invasion by upregulating the expression of β-catenin, MMP-2 and MMP-9, and decreased the expression of E-cadherin in the A549 cells. Our findings provide significant insight into the molecular mechanisms of lung cancer and offer novel ideas for designing new therapeutic targets for lung carcinoma.

Multidrug resistance (MDR) and multi-organ infiltration are the major obstacles to the successful treatment of leukemia. It is known that the drug efflux protein, P-glycoprotein (P-gp), and inhibitors of apoptosis proteins (IAPs) are involved in the MDR of leukemic cells, but their roles in leukemia infiltration have not been clearly elucidated. In this study, leukemic cell lines K562 and HL60 and their MDR variants K562R and HL60R have been used to analyze their infiltrative ability. MDR variants display enhanced invasion compared with parental cells. Results from xenografts in SCID (severe combined immunodeficiancy) mice are consistent with these in vitro observations. Furthermore, P-gp and cIAP are overexpressed and co-localize with protein kinase C-ε (PKC-ε) in MDR variants. Our study shows that overexpression of P-gp and cIAP may enhance the infiltration of leukemic cells.

The epithelial-mesenchymal transition (EMT) is a fundamental process governing morphogenesis in multicellular organisms and has recently been implicated in promoting carcinoma invasion and metastasis. Besides their therapeutic effects, accumulating evidences suggest that chemotherapeutic agents also induced EMT and enhanced the malignancy of treated cancer cells; however, the mechanism(s) still remains unclear. Here, we investigated the role of β-catenin signaling in doxorubicin (Dox)-induced EMT in human gastric cancer cell line BGC-823. We found that the transient treatment of Dox induced EMT and enhanced the in vitro migration ability of cancer cells. We also found that β-catenin signaling was activated upon Dox treatment. Inhibition of β-catenin by indomethacin (Indo) or siRNA suppressed Dox-induced EMT and decreased cancer cell migration ability. Our results showed that β-catenin signaling was critical to Dox-induced EMT. Indo and other β-catenin inhibitors may have a potential implication in prevention of gastric cancer metastasis.

Supplementary data are available at Bioinformatics online.