Biological function of C-X-C Motif Chemokine Ligand 1 gene (CXCL1) in ovarian malignant tumors.

OBJECTIVE: To determine the function of the chemokine (C-X-C motif) ligand 1 (CXCL1) gene in ovarian cancer cells and to investigate the relationship between CXCL1 gene mRNA expression and ovarian tumor clinical pathology. METHODS: Using bioinformatics methods to identify common differentially expressed genes associated with ovarian cancer in the GEO database. Growth curves of A2780 cells with or without CXCL1 expression were plotted by MTT assay. Cell cycles were measured by flow cytometry. Cell colony formation was enumerated in Transwell chambers. Migration and invasion in vitro were investigated using Cell Counting Kit-8 (CCK8), wound healing and Transwell, respectively. The relationship between CXCL1 gene mRNA expression and ovarian tumor clinical pathology was analyzed. RESULTS: CXCL1 was found to be one of the co-upregulated differentially expressed genes in the GEO database. The migration of A2780 cells expressing CXCL1 was significantly higher than that of A2780 cells without CXCL1 expression. CXCL1 mRNA expression in ovarian malignancy was significantly higher than those in benign lesions and the normal control (p < .01). In advanced ovarian cancer (Stages III-IV), CXCL1 mRNA expression was also significantly higher than that in patients with early-stage ovarian cancer (Stages I-II) (p = .005). Kaplan-Meier survival curve showed no correlation between CXCL1 mRNA expression and ovarian cancer prognosis. A Cox proportional hazard model also showed that CXCL1 expression was not an independent prognostic factor for ovarian cancer patients. CONCLUSIONS: CXCL1 gene could promotes ovarian cancer A2780 cell proliferation and invasion in vitro, and contributed theoretical knowledge for the target selection in molecular targeted therapy. CXCL1 mRNA over-expression may be correlated with the occurrence and development of ovarian malignancy. Level of plasma CXCL1 might serve as a biomarker for prognosis in ovarian carcinoma patients.

Current Progress of EMT: A New Direction of Targeted Therapy for Colorectal Cancer with Invasion and Metastasis.

Colorectal cancer (CRC) is a common malignant tumor with a high frequency of recurrence and metastasis, which are the major causes of death in patients. The prerequisite for the invasion and metastasis is the strong mobility of CRC cells to transport far away from the original site to the distant organs and tissues, where they settle down and proliferate. It was reported that the epithelial-mesenchymal transition (EMT) is involved in the occurrence and development of various tumors in the entire process of tumor invasion and metastasis. Therefore, as a vital factor for the biological characteristics of tumor cells, EMT markers may serve as prognostic predictors and potential therapeutic targets in CRC. This article mainly reviews the current status of CRC with metastasis, the studies of EMT, the possible relationship of EMT with CRC, as well as the potential targeted therapy.

Insights into the antitumor mechanism of ginsenosides Rg3.

Panax ginseng, an ancient herb, belonging to Chinese traditional medicine, is an important herb that has a remarkable impact on various diseases. Ginsenoside Rg3, one of the most abundant ginsenosides, exerts significant functions in the prevention of various types of cancers with few side effects. In the present review, its functional molecular mechanisms are explored, including the improvement of antioxidant and anti-inflammation properties, immune regulation, induction of tumor apoptosis, prevention of tumor invasion and metastasis, tumor proliferation and angiogenesis, and reduction of chemoresistance and radioresistance. On the other hand, metabolism, pharmacokinetics and clinical indications of Rg3 are also discussed. The biological functional role of ginsenoside Rg3 may be associated with that it is a steroid glycoside with diverse biological activities and many signaling pathway can be regulated. Many clinical trials are highly needed to confirm the functions of ginsenoside Rg3.

Phase separation as a therapeutic target in tight junction-associated human diseases.

Tight junctions (TJs) play an important role in the maintenance of epithelial and endothelial barriers. Zonula occludens (ZO) proteins are scaffolding molecules essential for the formation of TJ complexes, and abnormalities in ZO proteins have been implicated in various TJ-associated human diseases such as tumor invasion and metastasis, and barrier dysfunction. Recent studies reveal that liquid-liquid phase separation of ZO proteins drives the polymerization of TJ proteins into a continuous belt, which then recruits various proteins to form the TJ complex to regulate selective paracellular permeability and signal transduction. Herein, we describe recent advances on how ZO phase separation contributes to TJ formation and discuss the potential of phase separation as a target for the treatment of TJ-associated diseases.

GRP78 activates the Wnt/HOXB9 pathway to promote invasion and metastasis of hepatocellular carcinoma by chaperoning LRP6.

Recent studies have shown that the expression levels of glucose-regulated protein 78 (GRP78) and homeobox B9 (HOXB9) are both upregulated in hepatocellular carcinoma (HCC) and are closely related to HCC invasion and metastasis. However, whether there is a regulatory relationship between GRP78 and HOXB9 is unclear. In this study, we examined the expression of GRP78 and HOXB9 in HCC tissues and adjacent nontumor tissues. Correlation analysis indicated that GRP78 and HOXB9 expression were positively correlated. High levels of GRP78 and HOXB9 expression are closely related to worse clinicopathological features. Knockdown of GRP78 in HCC cells decreased the mRNA and protein expression of HOXB9, but increase HOXB9 expression reversed the decrease in invasion and metastasis induced by knocking down GRP78. Further experiments showed that GRP78 regulates HOXB9 through the Wnt signaling pathway by chaperoning low-density lipoprotein receptor-related protein 6 (LRP6). Importantly, we found that GPR78 promoted maturation of LRP6, while knockdown of GRP78 led to LRP6 misfolding and endoplasmic reticulum-associated degradation (ERAD). Consequently, the levels of mature LRP6 were reduced, and Wnt/HOXB9 signaling was inhibited. Our data suggest that the GRP78-LRP6-HOXB9 axis regulates the invasion and metastasis of HCC and may represent a potential therapeutic target for the treatment of HCC.

The mechanism of Annexin A1 regulating the proliferation, apoptosis and migration of bladder cancer cells / 中华泌尿外科杂志

Objective@#Explore the function and regulatory mechanism of Annexin A1 (ANXA1) in bladder cancer cell proliferation, apoptosis and migration.@*Methods@#From February 2018 to June 2019, we use T24 cells as the model and divide it into over-expression control group (ctrl), ANXA1 over-expression group (ANXA1), knockdown control group (shctrl), ANXA1 knockdown group 1 (shANXA1-1), ANXA1 knockdown group 2 (shANXA1-2) and ANXA1 knockdown group 3 (shANXA1-3). 24 hours after the culture, the cells were collected and the mRNA expression level of ANXA1 was detected by Real-Time quantitative PCR. The cell activity was detected by CCK-8; the cell apoptosis and cycle were detected by flow cytometry. The cell migration was detected by Transwell assay.@*Results@#The Real-Time quantitative PCR showed that the expression of ANXA1 in the over expression group was significantly higher than that in the over expression control group (15 369.00±874.20 and 1.00±0.07, P<0.001). The expression of ANXA1 in the knockdown group 2 and 3 were significantly lower than that in the knockdown control group (0.51±0.04, 0.51±0.02 and 1.00±0.04, P<0.001). Compared with the over expression control group(1.61±0.01), the cell activity of the over expression group(2.04±0.02)was significantly increased (P<0.001), while the activity of the knockdown group 2 and 3 (1.40±0.002 and 1.31±0.003)were significantly decreased than the knockdown ctrl group (1.73±0.01)(P<0.001). The results of flow cytometry showed that the number of G0/G1 cells in the over-expression group was significantly lower than that in the over-expression control group (28.14±0.33 and 46.19±0.73, P<0.001), while that in the knockdown group 2 and 3 were significantly higher than that in the knockdown control group (58.670±0.49, 62.34±4.01 and 45.59± 0.19, P<0.001 and P<0.05). There was no significant difference in the number of apoptosis between the over-expression group and the over-expression control group (P>0.05), while the number of apoptosis in the knockdown group 2 and 3 were significantly higher than that in the knockdown control group (13.04%, 14.58% and 7.76%, P<0.001). Cell function analysis showed that the number of cells passing through the membrane of the over expression group was significantly higher than that of the over expression group (525.00±9.30 and 385.70±13.40, P<0.01), while that of the knockdown group 2 and 3 were significantly lower than that of the knockdown control group (214.70±6.40, 226.00±5.30 and 398.70±10.00, P<0.001).@*Conclusions@#Over-expression of ANXA1 significantly promoted the proliferation, cycle and migration of T24 cells and inhibited apoptosis. On the contrary, ANXA1 knockdown inhibited the proliferation, cycle and migration of T24 cells and promoted apoptosis.

The mechanism of Annexin A1 regulating the proliferation, apoptosis and migration of bladder cancer cells / 中华泌尿外科杂志

Objective Explore the function and regulatory mechanism of Annexin A1 (ANXA1) in bladder cancer cell proliferation,apoptosis and migration.Methods From February 2018 to June 2019,we use T24 cells as the model and divide it into over-expression control group (ctrl),ANXA1 over-expression group (ANXA1),knockdown control group (shctrl),ANXA1 knockdown group 1 (shANXA1-1),ANXA1 knockdown group 2 (shANXA1-2) and ANXA1 knockdown group 3 (shANXA1-3).24 hours after the culture,the cells were collected and the mRNA expression level of ANXA1 was detected by Real-Time quantitative PCR.The cell activity was detected by CCK-8;the cell apoptosis and cycle were detected by flow cytometry.The cell migration was detected by Transwell assay.Results The Real-Time quantitative PCR showed that the expression of ANXA1 in the over expression group was significantly higher than that in the over expression control group (15 369.00 ± 874.20 and 1.00 ± 0.07,P ＜ 0.001).The expression of ANXA1 in the knockdown group 2 and 3 were significantly lower than that in the knockdown control group (0.51 ± 0.04,0.51 ± 0.02 and 1.00 ± 0.04,P ＜ 0.001).Compared with the over expression control group (1.61 ± 0.01),the cell activity of the over expression group(2.04 ± 0.02) was significantly increased (P ＜ 0.001),while the activity of the knockdown group 2 and 3 (1.40 ± 0.002 and 1.31 ± 0.003) were significantly decreased than the knockdown ctrl group (1.73 ± 0.01) (P ＜ 0.001).The results of flow cytometry showed that the number of G0/G1 cells in the over-expression group was significantly lower than that in the over-expression control group (28.14 ± 0.33 and 46.19 ± 0.73,P ＜ 0.001),while that in the knockdown group 2 and 3 were significantly higher than that in the knockdown control group (58.670 ± 0.49,62.34 ± 4.01 and 45.59 ± 0.19,P ＜ 0.001 and P ＜ 0.05).There was no significant difference in the number of apoptosis between the over-expression group and the over-expression control group (P ＞ 0.05),while the number of apoptosis in the knockdown group 2 and 3 were significantly higher than that in the knockdown control group (13.04％,14.58％ and 7.76％,P ＜ 0.001).Cell function analysis showed that the number of cells passing through the membrane of the over expression group was significantly higher than that of the over expression group (525.00 ± 9.30 and 385.70 ± 13.40,P ＜ 0.01),while that of the knockdown group 2 and 3 were significantly lower than that of the knockdown control group (214.70 ± 6.40,226.00 ± 5.30 and 398.70 ± 10.00,P ＜ 0.001).Conclusions Over-expression of ANXA1 significantly promoted the proliferation,cycle and migration of T24 cells and inhibited apoptosis.On the contrary,ANXA1 knockdown inhibited the proliferation,cycle and migration of T24 cells and promoted apoptosis.

Gene silencing of heparanase results in suppression of invasion and migration of gallbladder carcinoma cells.

This study investigated the effect of transcriptional gene silencing of the heparanase gene on standard gallbladder carcinoma cells (GBC-SD). The miRNAs targeting the promoter region and coding region of the heparanase gene were designed and synthesized. We transfected four recombinant miRNA vectors into GBC-SD. We performed the wound healing assays and invasion assays. The result shows that the heparanase expression was significantly decreased by recombinant vectors in transfected GBC-SD cells (p < 0.01), of which pmiR-Hpa-2 showed best interference effect (p < 0.05). The penetrated and migrating cells numbers and adherence rate of GBC-SD cells were significantly decreased by pmiR-Hpa-2 (p < 0.05).

Forecast of actin-binding proteins as the oncotarget in osteosarcoma - a review of mechanism, diagnosis and therapy.

Osteosarcoma (OS) is the most common bone malignant tumor with a high rate of lung metastasis and principally emerges in children and adolescents. Although neoadjuvant chemotherapy is widely used around the world, a high rate of chemoresistance occurs and frequently generates a poor prognosis. Therefore, finding a new appropriate prognostic marker for OS is a valuable research direction, which will give patients a better chance to receive proper therapy. Actin-binding proteins (ABPs) are a group of proteins that interact with actin cytoskeleton and play a crucial role in the regulation of the cell motility and morphology in eukaryotes. Meanwhile, ABPs also act as a bridge between the cytomembrane and nucleus, which transmit the outside-in and inside-out signals in cytoplasm. Furthermore, ABPs alter the dynamic structure of actin and regulate the invasion and metastasis of cancer. Hence, ABPs have a wide application in predicting the prognosis, and may be new targets, in tumor therapy. This review focuses on a series of ABPs and discusses their modulatory functions. It provides a new insight into the classification of ABPs' functions in the process of invasion and metastasis in OS and illuminates the potential ability in predicting the prognosis of OS patients.

Association between SNPs in microRNA machinery genes and gastric cancer susceptibility, invasion, and metastasis in Chinese Han population.

OBJECTIVE: The present study investigates the influence of genetic variants in miRNA machinery genes (DROSHA, DICER, AGO1, and GEMIN4) on gastric cancer in Chinese Han population, further revealing the genetic mechanisms of gastric cancer occurrence and development. METHODS: Genotyping of single nucleotide polymorphisms (SNPs) was performed in 628 patients with GC and 502 frequency-matched (age and gender) controls by the high resolution melting (HRM) method. RESULTS: The SNPs rs3742330 (DICER) and rs7813 (GEMIN4) were associated with susceptibility to gastric cancer (P = 0.002 and 0.010, respectively). Stratified analysis showed that the G allele of rs3742330 and genotype TT as well as T allele of rs7813 were associated with a later stage of gastric cancer (P=0.027, 0.032 and 0.018, respectively). Furthermore, the genotype TT and T allele of rs7813 appeared to be associated with a higher level of lymphatic metastasis of gastric cancer (P=0.021 and 0.030, respectively), while the genotype AA and A allele of rs636832 (AGO1) were correlated with a lower level of lymphatic metastasis of gastric cancer (P=0.016 and 0.041, respectively). There was no significant association between rs10719 (DROSHA) and gastric cancer. CONCLUSION: The present data demonstrated that genetic variants in miRNA machinery genes had a significant association with GC susceptibility (DICER and GEMIN4) and malignant behavior such as tumor stage (DICER and GEMIN4) and lymphatic metastasis of GC (GEMIN4 and AGO1) in Chinese Han population.

T-cell immunoglobulin mucin-3 expression in invasive ductal breast carcinoma: Clinicopathological correlations and association with tumor infiltration by cytotoxic lymphocytes.

As a negative regulatory molecule, T-cell immunoglobulin and mucin domain-3 (Tim-3) is closely associated with tumor immunological tolerance. The aim of this study was to investigate Tim-3 expression in invasive ductal breast cancer (IDC), its effect on clinicopathological parameters and its association with cytotoxic lymphocyte infiltration. Tim-3 protein expression was measured in 150 paraffin-embedded IDC specimens and 100 paired normal breast tissue specimens by immunohistochemistry. It was demonstrated that the infiltration of the tumor by CD8+ T cells was significantly higher compared with that of normal tissue, and the Tim-3 expression on CD8+ T cells was higher in IDC tissue compared with that in normal tissue; the differences were statistically significant (both P-values=0.000). The median expression level of Tim-3 on tumor cells was significantly associated with clinicopathological parameters such as age, axillary lymph node metastasis and TNM stage (P=0.015, 0.001 and 0.027, respectively). The expression of Tim-3 on CD8+ T cells was correlated with lymph node metastasis, World Health Organization (WHO) grade and molecular classification (P=0.000, 0.004 and 0.000, respectively). Additionally, the number of tumor-infiltrating CD8+ T cells was associated with primary tumor size, lymph node metastasis, WHO grade, Ki-67 and molecular classification (P=0.017, 0.002, 0.007, 0.003 and 0.000, respectively). Thus, Tim-3 may promote the development and progression of breast cancer and affect the tumor microenvironment; thus, it may be used as an independent prognostic factor for IDC patients.

The Emerging Role of Polo-Like Kinase 1 in Epithelial-Mesenchymal Transition and Tumor Metastasis.

Polo-like kinase 1 (PLK1) is a serine/threonine kinase that plays a key role in the regulation of the cell cycle. PLK1 is overexpressed in a variety of human tumors, and its expression level often correlates with increased cellular proliferation and poor prognosis in cancer patients. It has been suggested that PLK1 controls cancer development through multiple mechanisms that include canonical regulation of mitosis and cytokinesis, modulation of DNA replication, and cell survival. However, emerging evidence suggests novel and previously unanticipated roles for PLK1 during tumor development. In this review, we will summarize the recent advancements in our understanding of the oncogenic functions of PLK1, with a focus on its role in epithelial-mesenchymal transition and tumor invasion. We will further discuss the therapeutic potential of these functions.

Hormophysa triquerta polyphenol, an elixir that deters CXCR4- and COX2-dependent dissemination destiny of treatment-resistant pancreatic cancer cells.

Therapy-resistant pancreatic cancer (PC) cells play a crucial role in tumor relapse, recurrence, and metastasis. Recently, we showed the anti-PC potential of an array of seaweed polyphenols and identified efficient drug deliverables. Herein, we investigated the benefit of one such deliverable, Hormophysa triquerta polyphenol (HT-EA), in regulating the dissemination physiognomy of therapy-resistant PC cells in vitro,and residual PC in vivo. Human PC cells exposed to ionizing radiation (IR), with/without HT-EA pre-treatment were examined for the alterations in the tumor invasion/metastasis (TIM) transcriptome (93 genes, QPCR-profiling). Utilizing a mouse model of residual PC, we investigated the benefit of HT-EA in the translation regulation of crucial TIM targets (TMA-IHC). Radiation activated 30, 50, 15, and 38 TIM molecules in surviving Panc-1, Panc-3.27, BxPC3, and MiaPaCa-2 cells. Of these, 15, 44, 12, and 26 molecules were suppressed with HT-EA pre-treatment. CXCR4 and COX2 exhibited cell-line-independent increases after IR, and was completely suppressed with HT-EA, across all PC cells. HT-EA treatment resulted in translational repression of IR-induced CXCR4, COX2, ß-catenin, MMP9, Ki-67, BAPX, PhPT-1, MEGF10, and GRB10 in residual PC. Muting CXCR4 or COX2 regulated the migration/invasion potential of IR-surviving cells, while forced expression of CXCR4 or COX2 significantly increased migration/invasion capabilities of PC cells. Further, treatment with HT-EA significantly inhibited IR-induced and CXCR4/COX2 forced expression-induced PC cell migration/invasion. This study (i) documents the TIM blueprint in therapy-resistant PC cells, (ii) defines the role of CXCR4 and COX2 in induced metastatic potential, and (iii) recognizes the potential of HT-EA in deterring the CXCR4/COX2-dependent dissemination destiny of therapy-resistant residual PC cells.

Down-regulation of SDF1-α expression in tumor microenvironment is associated with aspirin-mediated suppression of the pro-metastasis effect of sorafenib in hepatocellular carcinoma.

Sorafenib is considered to be the first-line therapy for advanced hepatocellular carcinoma (HCC). It significantly delays tumor progression time; however, it increases the invasive and metastatic potential of HCC. Recent studies have shown that aspirin is effective in preventing and treating tumors, and the combination treatment of aspirin and sorafenib significantly suppresses sorafenib-induced intrahepatic metastasis. However, the mechanism through which aspirin suppresses the sorafenib-induced intrahepatic metastasis is still unclear. In this study, we find that sorafenib markedly increases stromal-derived factor 1-alpha (SDF1-α) expression in paratumor and intratumor tissues, and aspirin attenuates sorafenib-induced increase of SDF1-α expression in paratumor and intratumor tissues. Further studies show that SDF1-α improves cell invasion potential of HCC cells, and that AMD3100, a specific inhibitor of SDF1-α receptor CXCR4, suppresses the elevated intrahepatic metastatic potential of HCC induced by sorafenib in vivo. Collectively, this study reveals that the sorafenib-induced increase of SDF1-α expression in paratumor and intratumor microenvironments is suppressed by aspirin, which is associated with aspirin-mediated suppression of the pro-metastasis effect of sorafenib in HCC.

URGCP promotes non-small cell lung cancer invasiveness by activating the NF-κB-MMP-9 pathway.

Invasion and metastasis are main traits of tumor progression and responsible for the poor prognosis of advanced non-small cell lung cancer (NSCLC). The molecular mechanisms underlying the malignant behaviors of NSCLC remain incompletely understood. The present study demonstrate that up-regulator of cell proliferation (URGCP), a recently identified tumor-promoting gene found in several tumor types, is markedly overexpressed in human NSCLC cell lines and clinical NSCLC samples. URGCP upregulation correlates significantly with the progression and poor prognosis of this disease. In vitro and in vivo studies demonstrate that increasing URGCP expression accelerates invasion, migration, and distant metastasis of NSCLC cells whereas downregulating URGCP suppresses these malignant traits. Notably, silencing URGCP expression almost completely abrogates the metastatic ability of NSCLC cells. At the molecular level, URGCP markedly promotes MMP-9 expression by activating NF-κB signaling. Additionally, URGCP and MMP-9 expression are positively correlated in various cohorts of human NSCLC specimens, and NF-κB-activated MMP-9 expression contributes to URGCP-induced invasiveness of NSCLC cell lines. Collectively, these findings indicate that URGCP plays an important role in promoting NSCLC cell invasion and metastasis by enhancing NF-κB-activated MMP-9 expression and may serve as a potential therapeutic target and prognostic marker.

Overexpression of c-fos promotes cell invasion and migration via CD44 pathway in oral squamous cell carcinoma.

BACKGROUND: Oral squamous cell carcinoma (OSCC) is one of the most deadly malignant tumors with high invasive potential and frequently cervical lymph node metastasis. AP-1 plays a critical role in tumor invasion and metastasis, but there are few reports on the role of c-Fos in OSCC carcinogenesis and metastasis. METHODS: Investigate c-Fos expression in clinical samples from 58 primary patients with OSCC by immunohistochemistry. c-Fos knockdown stable cell lines were established by lentiviral infection and transwell cell invasion assay to detect the effects of c-Fos knockdown on tumor cell invasion. RESULTS: Nuclear and cytoplasmic c-Fos protein were both overexpression in cancerous tissues compared with adjacent non-malignant epithelia (nuclear: P < 0.001, cytoplasmic: P = 0.005). Higher level nuclear c-Fos expression was found in the tumor samples of patients with lymph node metastasis than those without lymph node metastasis (4.85 ± 1.43 vs. 3.61 ± 1.28, P = 0.002). Higher level of c-Fos expression was also found in tumor invasive front margin than tumor center and high nuclear expression of c-Fos indicated poor survival. Knockdown of c-Fos greatly suppressed tumor cell proliferation and invasion and downregulated CD44 and CyclinD1 expression in HN6 and SCC9 cells. However, CyclinD3, c-myc, and Erk1/2 were found no changes to c-Fos depletion. CONCLUSIONS: c-Fos promoted cell invasion and migration via CD44 pathway in OSCC. c-Fos could be used as a potential therapeutic target gene and an additional marker for evaluation of lymph node metastasis.

The expression and significance of Slug,EMMPRIN and E-cadherin in salivary adenoid cystic carcinoma / 实用口腔医学杂志

Objective:To investigate the expression of Slug,EMMPRIN and E-cadherin in salivary adenoid cystic carcinoma (SACC)and its correlation with clinicopathological characteristics,and the correlation among themselves.Methods:Slug,EMMPRIN and E-cadherin expression in 1 1 5 SACC cases of SACC was examined by immunohistochemical staining.The results and clinicopatho-logical data were statistically analyzed.Results:High positive expression frequencies of Slug(76.5%)and EMMPRIN(69.6%)and low positive expression frequency of E-cadherin(51 .3%)were found in 1 1 5 SACC cases.The expression of Slug and EMMPRIN was positively associated with the histopathological types,clinical stages,perineural invasion,recurrence and distance metastasis(P <0.05).The expression of E-cadherin was negatively associated with the histopathological types,clinical stages,perineural invasion and distance metastasis(P <0.05).There was a significant correlation between Slug and EMMPRIN expression(P <0.05),negative correlation between EMMPRIN and E-cadherin expression(P <0.05)and between Slug and E-cadherin expression(P <0.05).Con-clusion:The expression of Slug,EMMPRIN and E-cadherin is closely correlated to the clinicopathological characteristics of SACC.

Epithelial junctions and Rho family GTPases: the zonular signalosome.

The establishment and maintenance of epithelial cell-cell junctions is crucially important to regulate adhesion, apico-basal polarity and motility of epithelial cells, and ultimately controls the architecture and physiology of epithelial organs. Junctions are supported, shaped and regulated by cytoskeletal filaments, whose dynamic organization and contractility are finely tuned by GTPases of the Rho family, primarily RhoA, Rac1 and Cdc42. Recent research has identified new molecular mechanisms underlying the cross-talk between these GTPases and epithelial junctions. Here we briefly summarize the current knowledge about the organization, molecular evolution and cytoskeletal anchoring of cell-cell junctions, and we comment on the most recent advances in the characterization of the interactions between Rho GTPases and junctional proteins, and their consequences with regards to junction assembly and regulation of cell behavior in vertebrate model systems. The concept of "zonular signalosome" is proposed, which highlights the close functional relationship between proteins of zonular junctions (zonulae occludentes and adhaerentes) and the control of cytoskeletal organization and signaling through Rho GTPases, transcription factors, and their effectors.

Expression of peroxiredoxin 1 and 4 promotes human lung cancer malignancy.

Members of the Peroxiredoxin (Prx) family are major cellular antioxidants that scavenge hydrogen peroxide and play essential roles in oxidative stress and cell signaling. 2-Cys Prxs, including Prx1, 2, 3 and 4, have been indicated in multiple oncogenic signaling pathways and thus may contribute to various processes of cancer development. The significance of 2-Cys Prxs in lung cancer development and their biological function in signal transduction have not been fully investigated. In this study we analyzed the expression of 2-Cys Prxs in lung cancer, and examined their levels of expression in a variety of cell lines established from human lung normal or cancer tissues. We found that 2-Cys Prxs, in particular, Prx1 and Prx4, were preferentially expressed in cell lines derived from human lung cancer. Through isoform specific knockdown of individual Prx, we demonstrated that Prx1 and Prx4 (but not Prx3) were required for human lung cancer A549 cells to form soft agar colony and to invade through matrigel in culture. Knockdown of Prx1 or Prx4 significantly reduced the activation of c-Jun and repressed the AP-1 mediated promoter activity. In mouse xenograft models, knockdown of Prx4 in A549 cells reduced subcutaneous tumor growth and blocked metastasis formation initiated through tail vein injection. Moreover, overexpression of Prx1 or Prx4 further enhanced the malignancy of A549 cells both in culture and in mouse xenografts in vivo. These data provide an in-depth understanding of the contribution of Prx1 and Prx4 to lung cancer development and are of importance for future development of therapeutic methods that targeting 2-Cys Prxs.