The S-Nitrosylation of Septin2 (SNO-Septin2) axis: A novel potential therapeutic target for treating aneurysms and dissection.

Aortic aneurysm and aortic dissection (AAD) are severe life-threatening cardiovascular disorders for which no approved pharmaceutical therapies are currently available. Protein S-nitrosylation (SNO) is a typical redox-dependent posttranslational modification whose role in AAD has yet to be described. Recently, Zhang et al. revealed for the first time that SNO modification of macrophage cytoskeletal protein septin2 promotes vascular inflammation and extracellular matrix degradation in aortic aneurysm. Mechanically, the TIAM1-RAC1(T lymphoma invasion and metastasis-inducing protein 1-Ras-related C3 botulinum toxin substrate 1) axis participates in the progression of AAD induced with S-nitrosylated septin2. More importantly, developing R-ketorolac and NSC23766 compounds that specifically target the TIAM1-RAC1 pathway may be new a potential strategy for alleviating AAD.

Decreased Tiam1-mediated Rac1 activation is responsible for impaired directional persistence of chondrocyte migration in microtia.

The human auricle has a complex structure, and microtia is a congenital malformation characterized by decreased size and loss of elaborate structure in the affected ear with a high incidence. Our previous studies suggest that inadequate cell migration is the primary cytological basis for the pathogenesis of microtia, however, the underlying mechanism is unclear. Here, we further demonstrate that microtia chondrocytes show a decreased directional persistence during cell migration. Directional persistence can define a leading edge associated with oriented movement, and any mistakes would affect cell function and tissue morphology. By the screening of motility-related genes and subsequent confirmations, active Rac1 (Rac1-GTP) is identified to be critical for the impaired directional persistence of microtia chondrocytes migration. Moreover, Rho guanine nucleotide exchange factors (GEFs) and Rho GTPase-activating proteins (GAPs) are detected, and overexpression of Tiam1 significantly upregulates the level of Rac1-GTP and improves directional migration in microtia chondrocytes. Consistently, decreased expression patterns of Tiam1 and active Rac1 are found in microtia mouse models, Bmp5se/J and Prkralear-3J/GrsrJ. Collectively, our results provide new insights into microtia development and therapeutic strategies of tissue engineering for microtia patients.

Tiam1-mediated maladaptive plasticity underlying morphine tolerance and hyperalgesia.

Opioid pain medications, such as morphine, remain the mainstay for treating severe and chronic pain. Prolonged morphine use, however, triggers analgesic tolerance and hyperalgesia (OIH), which can last for a long period after morphine withdrawal. How morphine induces these detrimental side effects remains unclear. Here, we show that morphine tolerance and OIH are mediated by Tiam1-coordinated synaptic structural and functional plasticity in the spinal nociceptive network. Tiam1 is a Rac1 GTPase guanine nucleotide exchange factor that promotes excitatory synaptogenesis by modulating actin cytoskeletal dynamics. We found that prolonged morphine treatment activated Tiam1 in the spinal dorsal horn and Tiam1 ablation from spinal neurons eliminated morphine antinociceptive tolerance and OIH. At the same time, the pharmacological blockade of Tiam1-Rac1 signalling prevented the development and reserved the established tolerance and OIH. Prolonged morphine treatment increased dendritic spine density and synaptic NMDA receptor activity in spinal dorsal horn neurons, both of which required Tiam1. Furthermore, co-administration of the Tiam1 signalling inhibitor NSC23766 was sufficient to abrogate morphine tolerance in chronic pain management. These findings identify Tiam1-mediated maladaptive plasticity in the spinal nociceptive network as an underlying cause for the development and maintenance of morphine tolerance and OIH and provide a promising therapeutic target to reduce tolerance and prolong morphine use in chronic pain management.

TIAM-1 regulates polarized protrusions during dorsal intercalation in the Caenorhabditis elegans embryo through both its GEF and N-terminal domains.

Mediolateral cell intercalation is a morphogenetic strategy used throughout animal development to reshape tissues. Dorsal intercalation in the Caenorhabditis elegans embryo involves the mediolateral intercalation of two rows of dorsal epidermal cells to create a single row that straddles the dorsal midline, and thus is a simple model to study cell intercalation. Polarized protrusive activity during dorsal intercalation requires the C. elegans Rac and RhoG orthologs CED-10 and MIG-2, but how these GTPases are regulated during intercalation has not been thoroughly investigated. In this study, we characterized the role of the Rac-specific guanine nucleotide exchange factor (GEF) TIAM-1 in regulating actin-based protrusive dynamics during dorsal intercalation. We found that TIAM-1 can promote formation of the main medial lamellipodial protrusion extended by intercalating cells through its canonical GEF function, whereas its N-terminal domains function to negatively regulate the generation of ectopic filiform protrusions around the periphery of intercalating cells. We also show that the guidance receptor UNC-5 inhibits these ectopic filiform protrusions in dorsal epidermal cells and that this effect is in part mediated via TIAM-1. These results expand the network of proteins that regulate basolateral protrusive activity during directed rearrangement of epithelial cells in animal embryos.

Deficiency in SPOP-mediated ubiquitination and degradation of TIAM1 promotes gastric cancer progression.

It was well known that SPOP is highly mutated in various cancers especially the prostate cancer and SPOP mutation dramatically impaired its tumor suppressive function. However, the detailed role and underlying mechanisms of SPOP in regulating the growth of gastric cancer is not fully studied. Here, we found that Cullin3SPOP promoted the ubiquitination and degradation of TIAM1 protein in gastric cancer setting. Gastric cancer and prostate cancer derived SPOP mutation failed to suppress the proliferation, migration and invasion of gastric cancer cells partially due to the elevated level of TIAM1 protein. Notably, SPOP protein were negatively associated with TIAM1 protein in human gastric cancer tissue specimens. In conclusion, our results elucidate a molecular mechanism by which SPOP regulates the stability of TIAM1, and further demonstrate that SPOP inhibits the progression of gastric cancer by promoting the ubiquitination and degradation of TIAM1 protein.

Tiam1 methylation by NSD2 promotes Rac1 signaling activation and colon cancer metastasis.

Metastasis is a major cause of cancer therapy failure and mortality. However, targeting metastatic seeding and colonization remains a significant challenge. In this study, we identified NSD2, a histone methyltransferase responsible for dimethylating histone 3 at lysine 36, as being overexpressed in metastatic tumors. Our findings suggest that NSD2 overexpression enhances tumor metastasis both in vitro and in vivo. Further analysis revealed that NSD2 promotes tumor metastasis by activating Rac1 signaling. Mechanistically, NSD2 combines with and activates Tiam1 (T lymphoma invasion and metastasis 1) and promotes Rac1 signaling by methylating Tiam1 at K724. In vivo and in vitro studies revealed that Tiam1 K724 methylation could be a predictive factor for cancer prognosis and a potential target for metastasis inhibition. Furthermore, we have developed inhibitory peptide which was proved to inhibit tumor metastasis through blocking the interaction between NSD2 and Tiam1. Our results demonstrate that NSD2-methylated Tiam1 promotes Rac1 signaling and cancer metastasis. These results provide insights into the inhibition of tumor metastasis.

LNX1 inhibits the proliferation,invasion and migration of renal clear cell carcinoma cells by regulating TIAM1/ERK signaling pathway / 肿瘤

Objective:To investigate the effect of ligand of numb-protein X1(LNX1)on the proliferation,invasion and migration of renal clear cell carcinoma cells and its underlying molecular mechanism. Methods:Gene Expression Profiling Interactive Analysis(GEPIA)database was used to analyze the mRNA expression level of LNX1 in renal clear cell carcinoma tissues and its relationship with the prognosis of patients with renal clear cell carcinoma.LNX1 gene specific shRNA(shLNX1)was delivered into renal clear cell carcinoma cell lines 786-O and ACHN by lentiviral infection,and flag-LNX1 plasmid was delivered into 786-O and ACHN cells by transient transfection.CCK-8 assay and colony formation assay were used to assess the effects of LNX1 silencing or overexpression on the proliferation of 786-O and ACHN cells.Transwell assay was used to evaluate the effects of LNX1 silencing or overexpression on the invasion and migration of 786-O and ACHN cells.Bioinformatics analysis was used to screen the downstream target genes of LNX1.Western blotting was used to examine the effects of LNX1 silencing or overexpression on the expression level of T-lymphoma invasion and metastasis-inducing protein 1(TIAM1)as well as the expression levels of total and phosphorylated ERK(phospho-ERK,p-ERK)in the ERK signaling pathway downstream of TIAM1 in 786-O and ACHN cells.786-O and ACHN cells overexpressing LNX1 were treated with proteasome inhibitor MG132,and the protein expression level of TIAM1 was analyzed by Western blotting.Finally,myc-TIAM1 recombinant plasmid was transfected into LNX1-overexpressing cells.Then,the expression levels of proteins in the ERK signaling pathway and the abilities of proliferation,invasion and migration of 786-O and ACHN cells were examined by Western blotting,colony formation assay and Transwell assay,respectively. Results:The mRNA expression level of LNX1 in renal clear cell carcinoma tissue was decreased(P＜0.05)and was positively correlated with the survival time of patients with renal clear cell carcinoma(P＜0.001).LNX1-silencing 786-O and ACHN cells and LNX1-overexpressing 786-O and ACHN cells were constructed successfully.After LNX1 silencing,the proliferation,invasion and migration of 786-O and ACHN cells were significantly enhanced(all P＜0.05).After LNX1 overexpression,the abilities of proliferation,invasion and migration of 786-O and ACHN cells were significantly decreased(all P＜0.05).Bioinformatics analysis identified TIAM1 as a potential target of LNX1.After silencing LNX1,the protein expression levels of TIAM1 and p-ERK were significantly increased(all P＜0.05),while the expression level of ERK remained unchanged.After LNX1 overexpression,the protein expression levels of TIAM1 and p-ERKwere significantly decreased(all P＜0.01),while the expression level of ERK was unchanged.Treatment with proteasome inhibitor MG132 increased the protein expression level of TIAM1 in LNX1-overexpressing 786-O and ACHN cells(P＜0.01 and P＜0.001).After LNX1-overexpressing cells were transfected with myc-TIAM1 plasmid,the protein expression level of p-ERK was increased,the abilities of cell proliferation,invasion and migration were enhanced(all P＜0.05),and the expression level of ERK protein remained unchanged. Conclusion:LNX1 inhibits the proliferation,invasion and migration of renal clear cell carcinoma cells by degrading TIAM1 which further regulates the phosphorylation of ERK.

Prokaryotic expression and purification of Tiam1 truncated proteins / 医学研究生学报

Objective Tiam1, a member of guanine nucleotide exchange factors, plays an important role in tumor invasion and metastasis.This study aimed to construct Tiam1 truncated recombinant plasmids and induce the expression of GST-tagged human Tiam1 fusion proteins in Escherichia coli (E.coli), followed by purification and identification of the GST-Tiam1 fusion protein.Methods The cDNA fragments of Tiam1 C685, C751 and C1199 were amplified by PCR and cloned into the pGEX-4T-1 vector.After verified by DNA sequencing, the recombinant plasmid was transformed into E.coli BL21 (DE3) competent cells, and the expression of the fusion protein was induced by IPTG.The GST-tagged human Tiam1 fusion proteins were purified with glutathione-agarose resin and indentified by Western blot.Results Three Tiam1 truncated recombinant plasmids were constructed successfully.The recombinant fusion proteins GST-Tiam1 C685, GST-Tiam1 C751, and GST-Tiam1 C1199 were expressed mainly in the form of soluble proteins in the cell lysate supernatant with expected relative molecular weight of 100, 108, and 157 kD.Conclusion The recombinant plasmids expressing the bioactive fusion proteins were constructed successfully, which has prepared the ground for the subsequent studies of the Tiam1 protein.

Clinical implication of Tiam1 protein overexpression in ovarian carcinoma / 临床与实验病理学杂志

Purpose To investigate the clinicopathological significance of Tiam1 overexpression in ovarian carcinoma.Methods Tiam1 protein was detected in 98 serous carcinomas,64 ovarian mucinous cystadenocarcinomas and 27 benign ovarian tumors using immunohistochemical of SP two-step staining.Correlations between Tiam1 overexpression and clinicopathological features of ovarian carcinoma were evaluated.Overall survival and disease-free survival rates of ovarian carcinoma patients were calculated by Kaplan-Meier method.Results Tiam1 protein showed a cytoplasmic and nuclear staining pattern in ovarian carcinoma.The positive rate and strongly positive rate of Tiam1 protein were 84.7％ (83/98)and 70.4％ (69/98)in serous carcinoma,the positive rate and strongly positive rate of Tiam1 protein were 87.5％ (56/64) and 73.4％ (47/64) in ovarian mucinous cystadenocarcinoma,both of which were significantly higher than those in benign ovarian tumor (both P ＜ 0.01).High-level expression of Tiam1 was positively correlated with the histological grade,FIGO stage,and metastasis in ovarian carcinoma (both P ＜ 0.05),while independent of age and menopausal status (both P ＞ 0.05).Kaplan-Meier survival analysis showed that overall survival and disease-free survival of ovarian cancer patients with high expression of Tiam1 protein were significantly lower than those of patients with lower expression of Tiam1 protein (P ＜ 0.05),overall survival in metastatic ovarian cancer patients with high expression of Tiam1 protein was significantly lower than those in patients with low Tiam1 protein expression (P ＜ 0.05).Conclusion Tiam1 expression is significantly high in ovarian carcinoma.Tiam1 protein is closely associated with ovarian carcinoma progression,which may be a new potential prognostic biomarker and a therapeutic target for ovarian carcinoma.

Research progress on TIAM1 in pediatric neuroblastoma / 中国肿瘤临床

With continuous development of molecular diagnosis,"precision treatment"has entered the therapeutic category for ma-lignant tumors, and targeted gene therapy has been an intense research topic in recent years. Neuroblastoma is the most common ex-tracranial solid tumor that develops during childhood. Studies show that many genes, such as TIAM1, are involved in the development and progression of neuroblastoma. TIAM1 mainly combines with RAC1 to activate downstream factors that mediate differentiation via the TrkA/TIAM1/RAC1 signaling pathway, which is involved in the regulation of neurite. Therefore, further studies and experiments may reveal the specific mechanisms and provide a new direction for the future treatment and development of neuroblastoma.

Correlation between quantitative expression of T lymphoma invasion and metastasis inducing factor 1 mRNA and lymph node micrometastasis and prognosis in patients with colorectal cancer / 中华消化杂志

Objective To investigate the relationship between the changes of expression of T lymphoma invasion and metastasis inducing factor 1 (Tiam1) mRNA and lymph node micrometastasis and prognosis in patients with node-negative colorectal cancer(CRC).Methods From June 2008 to August 2010,a total of 63 patients with lymph node-negative CRC,20 patients with lymph node-positive CRC and 25 patients with colorectal benign lesions were enrolled.The relative quantity expression (RQ) of Tiam1 mRNA in CRC cancer tissues and colorectal benign lesions were detected by real-time quantitative polymerase chain reaction (PCR).The lymph node micrometastasis was determined by cytokeratin 20 detection in lymph nodes tissues.The five-year postoperative prognosis was evaluated by followed-up in the patients with lymph node-negative CRC.The correlation between the expression of Tiam1 mRNA and lymph node micrometastasis and prognosis was analyzed.The t-test,univariate analysis,multivariate analysis and Log-rank test were performed for statistical analysis.Results Lymphnode micrometastasis occurred in 33 from 63 patients with lymph node-negative CRC.The RQ of Tiam1 mRNA in the patients with lymph node-positive CRC was 9.84±-2.36,which was higher than that of patients with lymph node-negative CRC (5.15±3.58),and the difference was statistically significant (t=5.479,P＜0.01).The RQ of Tiam1 mRNA of these two groups were both higher than that of colorectal benign lesion (0.30± 0.21),and the difference was statistically significant(t=20.169,6.745;both P＜0.01).The RQ of Tiam1 mRNA of positive lymph node micrometastasis group was 6.30±1.95,which was higher than that of negative lymph node micrometastasis group (3.88 ± 1.63),and the difference was statistically significant (t=5.330,P＜0.01).In the patients with lymph node-negative CRC,the lower degree of tumor difference,the deeper invasion,the shorter survival time after surgery and postoperative recurrence and metastasis were related with the higher RQ of Tiam1 mRNA in tumor tissues (t=2.536,3.112,3.213,2.676;all P＜0.05).Univariate analysis revealed that the expression of Tiam1 mRNA in cancer tissues was correlated with lymph node micrometastases(x2=11.878,P =0.001).Multivariate analysis showed that it was an independent risk factors of lymph node micrometastases in CRC (relative risk:9.782).The five-year postoperative cumulative survival rate of high Tiaml mRNA expression group was 75.8 ％,which was lower than that of low expression group (97.1 ％),and the difference was statistically significant (x2 =4.575,P＜0.05).Conclusions Tiam1 may participate in the regulation of lymph node metastasis in CRC.Elevated expression of Tiam1 promotes lymph node metastasis and is closely relatived with poor prognosis of node-negative CRC,and which can be considered as an indicator of prognosis.

Screening of Tiam1-related genes contributing to metastasis of colorectal cancer using a gene expression profiling chip / 临床与实验病理学杂志

Purpose To screen and identify T cell lymphoma invasion and metastasis 1 (Tiam1) related genes and expression profile during distant metastasis of colorectal cancer. Methods Colorectal cancer( CRC) in a mice model was established by intraperitoneal injection of dimethylhydrazine ( DMH) . Five panels of fresh primary tumor tissues from Tiam1 transgenic mice were collected and com-pared with that from wild type mice. Differentially expressed genes were detected by Affymetrix human genome-wide expression profile chip and verified by real-time quantitative PCR ( qRT-PCR) analysis. Results The genechip result showed that 794 genes were differ-entially expressed by at least 3 folds in Tiam1 transgenic mice with distant metastasis of colorectal cancer tissue, including 400 up-regu-lated and 394 down-regulated ones. Bioinformatics analysis and gene co-expression network building identified 3 genes (PIK3R5, FIGF and RPS6KA6) with specific expression in colorectal cancer tissue with distant metastasis, and this result was confirmed by qRT-PCR. Conclusion A specific Tiam1 gene expression profile related to colorectal cancer distant metastasis has been established through screening and identifying the genes related to Tiam1 by gene chip technique. These findings provide a basis for exploring the molecular markers of colorectal cancer with distant metastasis.

Effects of Tiam1 overexpression on biological characters of human colorectal cancer cells / 实用医学杂志

Objective To explore the effect of Tiam1 overexpression on the biological behaviors of human colorectal cancer cells ( CRC ) . Methods The human CRC lines under the established stable overexpression of Tiam1 were studied. Cell morphology was detected before and after transfection by commassie blue staining and scanning electron microscope. The proliferation in vitro of CRC was tested by cell cycle, MTT and plate colony formation assay, the migration and invasion ability of CRC was tested by Transwell assay. The proliferation ability in vivo was studied by induced subcutaneous tumors of nude mice. Results Compared with HT29/mock cells, HT29/Tiam1 cells formed as spindle, the pseudopodia increased and elongated. The proportion in S phase of HT29/Tiam1 was higher (t=19.546, P=0.000), the proliferation ability enhanced (F=177.125, P=0.000), colonies formation ratio increased ( t = 3 . 222 , P = 0 . 032 ) . The number of HT29/Tiam1 cells acrossing the microporous membrane (t = 4.832, P=0.001)and Matrigel(t=3.779, P = 0.005)all raised. On the fifteenth day, the growth deference between the HT29/Tiam1cells and HT29/mock cells in nude mice in vivo occurred. Till the thirtieth day, the size of the tumors in HT29/Tiam1 cell group were 2.3 times as large as that in HT29/mock cell group (F=53.040, P=0.002). Conclusions Tiam1 stable overexpression can promote the proliferation, migration and invasion ability of CRC which indicates its important role in carcinogenesis and evolution of colorectal cancer. Tiam1 may represent a new therapeutic target for colorectal cancer.

Expression levels of Tiam-1 and HPA-1 and their relationship with the invasion and metastasis of hepatocellular carcinoma / 中国肿瘤临床

Objective: Invasion and metastasis are the main causes of carcinoma mortality; hence, the timely blocking of the invasion and metastasis of carcinoma has become a research hotspot. The present study aims to investigate the expression levels of Tiam-1 mRNA and HPA-1 mRNA and their correlation with the invasion and metastasis of hepatocellular carcinoma. Methods: From May 2009 to Jan 2012, 65 hepatocellular carcinoma patients admitted consecutively in our hospital for surgical treatment were included in this study. Real-time fluorescent quantitative reverse transcriptase polymerase chain reaction (RT-PCR) was used to investigate the expression levels of Tiam-1 mRNA and HPA-1 mRNA in hepatocellular carcinoma, paired adjacent hepatocellular carcinoma (2 cm from the carcinoma), and surgical marginal normal hepato mucosa tissues (5 cm from the carcinoma). RT-PCR was also used to analyze their correlation with the clinicopathological characteristics of hepatocellular carcinoma. Results: The expression level of HPA-1 mRNA was significantly higher in hepatocellular carcinoma (43.83±11.62) than in paired adjacent hepatocellular carcinoma (14.82±8.16) and normal hepato mucosa tissues (6.02±5.36) (P<0.001). The expression level of HPA-1 mRNA was higher in paired adjacent hepatocellular carcinoma than in normal hepato mucosa tissues (P<0.05). The expression of Tiam-1 mRNA was higher in hepatocellular carcinoma (35.28±11.81) than in paired adjacent hepatocellular carcinoma (12.94±6.25) and normal hepato mucosa tissues (4.17±3.49) (P<0.05). The expression level of Tiam-1 mRNA was higher in paired adjacent hepatocellular carcinoma than in normal hepato mucosa tissues (P<0.05). The expression levels of Tiam-1 mRNA and HPA-1 mRNA were closely associated with the degree of differentiation, depth of infiltration, lymph node metastasis, vessel metastasis, and TNM (Tumor, Node, Metastasis)staging of gastric carcinoma (P<0.05). Spearman rank correlation analysis demonstrated a significant correlation between Tiam-1 and HPA-1 (OR=0.523, P<0.05). Conclusion: The expression levels of Tiam-1 mRNA and HPA-1 mRNA were high in hepatocellular carcinoma. Meanwhile, the increased ex-pression levels of Tiam-1 and HPA-1 can promote the invasion and metastasis of hepatocellular carcinoma. Moreover, the determination of Tiam-1 and HPA-1 may be valuable for the treatment and prognosis of hepatocellular carcinoma.

Correlation between expression of TIAM1 gene and carcinomas of larynx / 临床检验杂志

Objective To study the relation between Tiam1 gene(T lymphoma invasion/metastasis 1)and carcinomas of larynx metastasized to lymph node.Method Using reverse transcription polymerase chain (RT-PCR) mRNA overexpression of Tiam1 gene in 30 cases of carcinoma of larynx tissue,12 lymph nodes and 10 cases of normal larynx tissue was studied.Result The frequency of TIAM1 overexpression was 75% (6/8) in primary carcinomas of larynx with metastasis but only 18.7%(4/22) in those without metastasis(P=0.0072).Overexpression of TIAM1 in metastasized lymph nodes was observed in 100% (8/8) of lymph nodes with metastasis but in only 25%(1/4) of the lymph nodes without metastasis of carcinoma(P=0.0182).The frequency of TIAM1 overexpression was 33.3% (10/30) in primary carcinomas of larynx.Conclusion Our data suggest that the overexpression of the TIAM1 gene correlates with lymph node metastasis of carcinomas of larynx.

Advances in the research on Tiam 1 and tumor invasion and metastasis / 中国癌症杂志

As a guanine nucleotide dissociation stimulator (GDS) of Rho-like GTPases, T lymphoma invasion and metastasis inducing factor 1(Tiam 1)possesses such biological functions as regulating reconstruction of cytoskeletal structure and migratory potential of cells. Studies had shown that over-expression of Tiam 1 was able to induce invasion and metastasis of tumor cells, the molecular biological basis of which includes the interactions between Tiam 1 and trans-membrane system of cytoskeleton, adhesion molecules and extra-cellular matrix, the effect on proliferation and apoptosis of tumor cells exposed by Tiam 1, as well as the activities of Tiam 1 regulated by other invasion and meatstasis associated factors. Simultaneously, these experimental results suggested that much more work would be needed in Tiam 1 on the diversity of its activity regulation ,the specificity of its biological effect, the realationship among Tiam 1 with other invasion and metastasis associated factors, as well as their mechanisms of signal transduction.

Relationship between the expression of Tiam1, Rac1 and the pathobiological behavior of gastric cancer / 中国普通外科杂志

Objective To investigate the relationship between the expression of T lymphoma invasion and (metastasis) inducing factor 1 (Tiam1), ras-related C3 botulinum toxin substrate 1 (Rac1) with the invasion and metastasis of gastric cancer. Methods The expressions of Tiam1 and Rac1 proteins in 60 cases of (gastric) cancer and paracarcioma gastric mucosa tissues were detected using Strept Avidin-Biotin Complex(SABC) immunohistochemical method,and the correlation between the expression of Tiam1, Rac1 and (clinicopathological) parameters of gastric cancer were analysed. Results (1)There was negative staining of Tiam1 protein in paracarcioma gastric mucosa tissues, while positive staining was detected in gastric cancer (tissues)(78.33%)(P 0.05). (4) The expression of Rac1 in patients with positive staining of Tiam1 was significantlyhigher than that in patients with negative staining(P