Ezrin, which crosslinks the cytoskeleton and plasma membrane, is involved in the growth and metastatic potential of cancer cells. Ezrin expression in esophageal squamous cell carcinoma (ESCC) was described recently, but its roles and the underlying mechanism(s) remain unclear. In our study, we first showed that ezrin in ESCC cell is expressed in the nucleus as well as in the cytoplasm and plasma membrane. Then, by using RNAi, we revealed that interference of ezrin expression suppressed the growth, adhesion and invasiveness of ESCC cells. Tumorigenesis experiments revealed that ezrin may directly regulate tumor formation in vivo.To explore the molecular mechanisms through which ezrin contributes to the proliferation and invasiveness of ESCC cells, we used cDNA microarrays to analyze ezrin knockdown cells and the control cells; of 39,000 genes examined, 297 were differentially expressed upon ezrin knockdown, including some proliferationand invasiveness-related genes such as ATF3, CTGF and CYR61. Furthermore, pathway analysis showed that ezrin knockdown led to decreased activation of the TGF-b and MAPK pathways, and ezrin-mediated cell invasiveness alteration was dependent on the activation of these pathways. Finally, immunohistochemical staining on 80 ESCC specimens and 50 normal esophageal mucosae revealed that the expression levels of 3 altered genes involved in the regulation of cell proliferation and tumor metastasis, including CTGF, CYR61 and ATF3, were altered in ESCCs, and their expression pattern correlated with ezrin expression. Taken together, we propose that ezrin might function in the growth and invasiveness of ESCC cells through the MAPK and TGF-b pathways. ' 2008 Wiley-Liss, Inc.Key words: ezrin; esophageal squamous carcinoma; growth and invasiveness; RNAi and cDNA microarrays; TGF-b; and MAPK pathways Esophageal squamous cell carcinoma (ESCC) is one of the most fatal malignancies worldwide. One of the reasons for its poor prognosis is that ESCC exhibits extensive local invasion or regional lymph node metastasis even at initial diagnosis.1,2 Metastatic tumors are often refractory or only partially sensitive to current therapeutic strategies and are the primary cause of cancerrelated mortality.3 Therefore, a better understanding of tumor dissemination and growth is paramount, and identification of the genes that are crucial for metastatic dissemination is of great interest not only for a basic understanding of the molecular and cellular processes involved but also to provide potential new therapeutic targets.Certain genes, MTA1 and Fascin, 4-6 have been proven to be involved in ESCC invasion. Our study focuses on ezrin, which was initially isolated as a cytoskeletal component of intestinal microvilli and a substrate for tyrosine kinase.7 As a member of the ezrin-radixin-moesin (ERM) protein family, ezrin acts both as a linker between the actin cytoskeleton and plasma membrane proteins and as a signal transducer in responses involving cytoskeletal remodeling.7 Furthermore, ezrin is present in the nucl...

Chemotherapy-induced neuropathic pain (CNP) is the major dose-limiting factor in cancer chemotherapy. However, the neural mechanisms underlying CNP remain enigmatic. Accumulating evidence implicates the involvement of spinal glia in some neuropathic pain models. In this study, using a vincristine-evoked CNP rat model with obvious mechanical allodynia, we found that spinal astrocyte rather than microglia was dramatically activated. The mechanical allodynia was dose-dependently attenuated by intrathecal administratration of L-α-aminoadipate (astrocytic specific inhibitor); whereas minocycline (microglial specific inhibitor) had no such effect, indicating that spinal astrocytic activation contributes to allodynia in CNP rat. Furthermore, oxidative stress mediated the development of spinal astrocytic activation, and activated astrocytes dramatically increased interleukin-1β expression which induced N-methyl-D-aspartic acid receptor (NMDAR) phosphorylation in spinal neurons to strengthen pain transmission. Taken together, our findings suggest that spinal activated astrocytes may be a crucial component of the pathophysiology of CNP and “Astrocyte-Cytokine-NMDAR-neuron” pathway may be one detailed neural mechanisms underlying CNP. Thus, inhibiting spinal astrocytic activation may represent a novel therapeutic strategy for treating CNP.

Long noncoding RNA (lncRNA) MEG3 is an important tumor suppressor in several types of human cancers. However, the biological function and underlying mechanism of MEG3 in vascular endothelial cells (VECs) remain unknown. In the present study, we demonstrated the functional importance of lncRNA MEG3 in proliferation and angiogenesis of VECs. MEG3 overexpression significantly suppressed the proliferation and in vitro angiogenesis in VECs, whereas knockdown of MEG3 had the opposite effect. Furthermore, we found that MEG3 exerts its function through negatively regulating miR-9 by acting as a microRNA sponge. Taken together, MEG3-miR-9 plays an important role in proliferation and angiogenesis in VECs.

Na+-dependent glucose cotransporter (SGLT1), reported overexpression in tumor tissues while its clinical significance was not established, and epidermal growth factor receptor (EGFR) with potential relation to SGLT1 were studied in order to investigate their clinical significance in colorectal cancer (CRC). Eighty-five patients of CRC who received chemotherapy in Sun Yat-sen Cancer Center from March 1st 2005 to December 31st 2008 were enrolled. SGLT1 and EGFR expression in these cancer tissues and 28 normal tissues were tested by immunohistochemistry. (1) Expression of SGLT1 (P = 0.00) and EGFR (P = 0.01) in cancer tissues was higher than that in normal tissues. (2) Their expression related with clinical stage (P = 0.03 and P = 0.02), but not with other clinical characteristics. (3) For first-line chemotherapy, expression of SGLT1 (P = 0.06 and P = 0.21) and EGFR (P = 0.37 and P = 0.31) had no influence on objective response rate (ORR) and disease control rate (DCR). EGFR overexpression was associated with lower disease-free survival (P = 0.00) and overall survival (P = 0.01), while SGLT1 did not (P = 0.79 and P = 0.34). Conclusions Both SGLT1 and EGFR overexpression in CRC was related to higher clinical stages. SGLT1 had a potential impact on the ORR of first-line chemotherapy in CRC. EGFR was associated with prognosis, while SGLT1 did not.