Genome-wide expression profile of sporadic gastric cancers with microsatellite instability

D’Errico, Mariarosaria; Rinaldis, Emanuele de; Blasi, Monica Francesca; Viti, Valentina; Falchetti, Mario; Calcagnile, A.; Sera, Francesco; Saieva, Calogero; Ottini, Laura; Palli, Domenico; Palombo, Fabio; Giuliani, Alessandro; Dogliotti, Eugenia

doi:10.1016/j.ejca.2008.10.032

Cited by 285 publications

(243 citation statements)

References 24 publications

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“…1A and B, Rac1 mRNA levels were found to be higher in all the subtypes of gastric cancer compared with paired non-tumor tissues or normal gastric mucosal tissues in Cho et al (29) and Wang et al (30) datasets. Furthermore, by comparing Rac1 mRNA levels within different subtypes based on Lauren's classification, all the available datasets showed Rac1 mRNA levels were higher in intestinal-type than diffuse-and mix-types in D'Errico et al (31), Ooi et al (32), and Foster et al (33) datasets (Fig. 1C).…”

Section: Resultsmentioning

confidence: 99%

Rac1 is correlated with aggressiveness and a potential therapeutic target for gastric cancer

Feng

Shi

et al. 2015

International Journal of Oncology

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Abstract. Rac1 is a member of the Rho GTPase family. Rac1 activity is critical in regulating cytoskeleton organization and thus, modulates a diverse spectrum of cellular functions in normal and malignant cells. The aims of the present study were to investigate the expression pattern and clinical significance of Rac1, as well as the role of Rac1 in gastric cancer tumorigenesis and metastasis. The expression of Rac1 in human gastric cancer was explored by immunohistochemistry. The correlation of Rac1 expression with the clinicopathological characteristics and the survival of patients were analyzed by Pearson's Chi-square and KaplanMeier analyses, respectively. Rac1 overexpression cell model was used to examine in vitro and in vivo effects of Rac1 in cell growth, migration and invasion. Rac1 was highly expressed in gastric cancer tissues and correlated with differentiation, local invasion, lymph node metastasis and Lauren's classification. Rac1 expression in gastric cancer predicted shorter survival. Overexpression of Rac1 in gastric cancer cells dramatically induced Rac1 activation and rendered a more aggressive phenotype such as increased cell growth and migration/invasion in vitro and in vivo. Inhibiting Rac1 activity by specific inhibitor abrogated the effects of Rac1 on the malignant phenotype. Our clinical findings demonstrated that Rac1 was well correlated with aggressiveness and a negative prognostic factor. In addition, our data on experimental cell models supported the fundamental role of Rac1 in gastric cancer. Given its pivotal role in gastric tumorigenesis and progression, Rac1 can serve as a promising therapeutic target for gastric cancer.

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Section: Resultsmentioning

confidence: 99%

Rac1 is correlated with aggressiveness and a potential therapeutic target for gastric cancer

Feng

Shi

et al. 2015

International Journal of Oncology

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“…1, and data not shown). Compared with normal tissues, STX6 expression is elevated in breast, colon, liver, pancreatic, prostate, bladder, skin, testicular, tongue, cervical, lung and gastric cancers (Biewenga et al, 2008;D'Errico et al, 2009;Hou et al, 2010;Kaiser et al, 2007;Korkola et al, 2006;LaTulippe et al, 2002;Richardson et al, 2006;Riker et al, 2008;Sanchez-Carbayo et al, 2006;Segara et al, 2005;Wurmbach et al, 2007;Ye et al, 2008) (Fig. 1).…”

Section: Stx6 Is Overexpressed In Cancersmentioning

confidence: 99%

“…cDNA of human STX6 was amplified by PCR from an I.M.A.G.E. clone and cloned into the pCMV-3Tag-1a vector to generate a construct that encodes an (Richardson et al, 2006); 5 normal colon, 17 cecum adenocarcinoma (Kaiser et al, 2007); 10 normal liver, 35 hepatocellular carcinoma (Wurmbach et al, 2007); 6 normal pancreas, 11 pancreatic carcinoma (Segara et al, 2005); 3 normal prostate gland, 32 prostate carcinoma (LaTulippe et al, 2002); 48 normal bladder, 81 bladder urothelial carcinoma (Sanchez-Carbayo et al, 2006); 4 normal skin, 11 skin squamous cell carcinoma (Riker et al, 2008); 6 normal testis, 101 adult male germ cell tumor (Korkola et al, 2006); 12 normal tongue, 26 tongue squamous cell carcinoma (Ye et al, 2008); 5 normal cervix, 40 cervical squamous cell carcinoma (Biewenga et al, 2008); 65 normal lung, 27 squamous cell lung carcinoma (Hou et al, 2010); and 31 normal gastric mucosa, 4 gastric adenocarcinoma (D'Errico et al, 2009) samples was analyzed using microarrays. Dark gray boxes represent tumor tissues and light gray boxes represent normal tissues.…”

Section: Stx6 Overexpression Stimulates Cell Migration Spreading Andmentioning

confidence: 99%

Regulation of Integrin Endocytic Recycling and Chemotactic Cell Migration by Syntaxin 6 and VAMP3 Interaction

Riggs

Hasan

Humphrey

et al. 2012

Journal of Cell Science

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SummaryIntegrins are the primary receptors of cells adhering to the extracellular matrix, and play key roles in various cellular processes including migration, proliferation and survival. The expression and distribution of integrins at the cell surface is controlled by endocytosis and recycling. The present study examines the function of syntaxin 6 (STX6), a t-SNARE located in the trans-Golgi network, in integrin trafficking. STX6 is overexpressed in many types of human cancer. We show that depletion of STX6 inhibits chemotactic cell migration and the delivery of the laminin receptor a3b1 integrin to the cell surface, whereas STX6 overexpression stimulates chemotactic cell migration, integrin delivery, and integrin-initiated activation of focal adhesion kinase. These data indicate that STX6 plays a ratelimiting role in cell migration and integrin trafficking. In STX6-depleted cells, a3b1 integrin is accumulated in recycling endosomes that contain the v-SNARE VAMP3. Importantly, we show that STX6 and VAMP3 form a v-/t-SNARE complex, VAMP3 is required in a3b1 integrin delivery to the cell surface, and endocytosed a3b1 integrin traffics to both VAMP3 and STX6 compartments. Collectively, our data suggest a new integrin trafficking pathway in which endocytosed integrins are transported from VAMP3-containing recycling endosomes to STX6-containing trans-Golgi network before being recycled to the plasma membrane.

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“…SerpinB5 acts as a tumor suppressor through its binding partners, which include tissuetype plasminogen activator (19), types I and III collagen (20), interferon regulatory factor 6 (IRF6) (21), glutathione s-transferase (GST) (22), pro-uPA (23), histone deacetylase 1 (HDAC1) (24), nuclear IKKalpha (25), PTEN, p53 (26), and testisin (27). However, SerpinB5 is believed to be an oncogene in GC, and the expression profiles of SerpinB5 in different types of GC have been extensively examined (2,3,28,29). Our data show that SerpinB5 might act as an oncogene though its interaction with KHDRBS3 and FBXO32.…”

Section: Discussionmentioning

confidence: 99%

SerpinB5 interacts with KHDRBS3 and FBXO32 in gastric cancer cells

Lei

Liu²,

Wang³

et al. 2011

Oncol Rep

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Abstract. Mammary serine protease inhibitor B5 (SerpinB5) is a potential oncogene in gastric cancer (GC); however, the molecular mechanism by which SerpinB5 promotes oncogenesis remains elusive. In this study, SerpinB5-associated proteins were selected based on yeast two-hybrid screening and microarray analysis after RNA interference and were validated using co-immunoprecipitation (Co-IP) and RNA Co-IP. The expression profiles of the interacting proteins were analyzed by Western blotting and immunohisto chemistry. The effects of SerpinB5 on KHDRBS3 and FBXO32 expression in GC cells were analyzed using real-time PCR and Western blotting after the expression of SerpinB5 was modified. By yeast two-hybrid screening and microarray analysis, FBXO32 and KHDRBS3 were found to be SerpinB5-interacting proteins. The interactions were confirmed by Co-IP. An RNA co-immunoprecipitation assay found that KHDRBS3 interacted with FBXO32 mRNA. The expression of SerpinB5 was much stronger in the nucleus of GC cells. FBXO32 was expressed at higher levels in the cytoplasm of GC cells. KHDRBS3 was primarily detected in the nucleus of normal mucosal cells. SerpinB5 expression was modified in GC cells, KHDRBS3 mRNA levels remained stable, however, FBXO32 mRNA levels changed 24 h after changes in KHDRBS3 protein levels were detected. In conclusion, SerpinB5 interacts with KHDRBS3 and FBXO32, and KHDRBS3 can interact with FBXO32 mRNA. IntroductionMammary serine protease inhibitor B5 (SerpinB5) is a 42-kDa protein that is a member of the ovalbumin clade of serine protease inhibitors (serpins). SerpinB5 was identified by subtractive hybridization and differential display, and was found to be expressed in normal mammary epithelial cells but not in most mammary carcinoma cell lines, and was considered to be a tumor suppressor (1).However, conflicting reports on its function in cancer occurrence and progression have been reported. Gastric tumor specimens showed increasing SerpinB5 expression level compared to corresponding normal tissues. The frequency of SerpinB5 induction was associated with the stage of gastric cancer (GC) and lymph node metastasis. SerpinB5 may have an important role in the progression and metastasis of gastric adenocarcinoma (2,3).The function of SerpinB5 and its significance have not been fully elucidated in human GC. The focus of this study was to identify SerpinB5-associated molecules. Using RNA interference techniques, microarray and yeast two-hybrid screening, we found that KHDRBS3 and FBXO32 specifically interacted with SerpinB5. These results not only suggest a possible mechanism for SerpinB5 in GC but also provide new avenues for SerpinB5-based drug development. Materials and methodsChemicals and reagents. Antibodies were purchased from commercial sources and included SerpinB5 monoclonal antibody (Novocastra, UK), TTK (N1) monoclonal antibody (Santa Cruz Biotechnology, USA), FBXO32 polyclonal antibody (Santa Cruz Biotechnology), KHDRBS3 polyclonal antibody (Santa Cruz Biotechnology), DDX18 polyclonal antibody (Abn...

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Genome-wide expression profile of sporadic gastric cancers with microsatellite instability

Cited by 285 publications

References 24 publications

Rac1 is correlated with aggressiveness and a potential therapeutic target for gastric cancer

Rac1 is correlated with aggressiveness and a potential therapeutic target for gastric cancer

Regulation of Integrin Endocytic Recycling and Chemotactic Cell Migration by Syntaxin 6 and VAMP3 Interaction

SerpinB5 interacts with KHDRBS3 and FBXO32 in gastric cancer cells

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