Elmo1 Helps Dock180 to Regulate Rac1 Activity and Cell Migration of Ovarian Cancer

Wang, Jin; Dai, Jie-Min; Che, Ya-ling; Gao, Yimeng; Peng, Huijuan; Liu, Bin; Wang, Hui; Linghu, Hua

doi:10.1097/igc.0000000000000137

Cited by 21 publications

(20 citation statements)

References 22 publications

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“…This protein acts as a guanine nucleotide exchange factor (GEF) for the Rho GTPases (a protein family of small guanosine triphosphates), by signaling the exchange of GDP (guanosine diphosphatase) for free GTP (guanosine-5’–triphosphate). The GEF activity requires binding with engulfment and cell motility 1 protein (ELMO1) [ 107 , 108 ] to form a bipartite complex, which increases stability for DOCK1 activity toward GTPase Rac1 [ 109 ] in several biological processes, such as endothelial apoptosis [ 108 ], cytoskeletal organization [ 110 – 112 ], cell migration and invasion [ 113 – 115 ], tumor cell motility and invasion [ 116 , 117 ], and phagocytosis [ 118 ].…”

Section: Resultsmentioning

confidence: 99%

Genome-Wide Association Study between Single Nucleotide Polymorphisms and Flight Speed in Nellore Cattle

Valente¹,

Baldi²,

Sant’Anna³

et al. 2016

PLoS ONE

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IntroductionCattle temperament is an important factor that affects the profitability of beef cattle enterprises, due to its relationship with productivity traits, animal welfare and labor safety. Temperament is a complex phenotype often assessed by measuring a series of behavioral traits, which result from the effects of multiple environmental and genetic factors, and their interactions. The aims of this study were to perform a genome-wide association study and detect genomic regions, potential candidate genes and their biological mechanisms underlying temperament, measured by flight speed (FS) test in Nellore cattle.Materials and MethodsThe genome-wide association study (GWAS) was performed using a single-step procedure (ssGBLUP) which combined simultaneously all 16,600 phenotypes from genotyped and non-genotyped animals, full pedigree information of 162,645 animals and 1,384 genotyped animals in one step. The animals were genotyped with High Density Bovine SNP BeadChip which contains 777,962 SNP markers. After quality control (QC) a total of 455,374 SNPs remained.ResultsHeritability estimated for FS was 0.21 ± 0.02. Consecutive SNPs explaining 1% or more of the total additive genetic variance were considered as windows associated with FS. Nine candidate regions located on eight different Bos taurus chromosomes (BTA) (1 at 73 Mb, 2 at 65 Mb, 5 at 22 Mb and 119 Mb, 9 at 98 Mb, 11 at 67 Mb, 15 at 16 Mb, 17 at 63 Kb, and 26 at 47 Mb) were identified. The candidate genes identified in these regions were NCKAP5 (BTA2), PARK2 (BTA9), ANTXR1 (BTA11), GUCY1A2 (BTA15), CPE (BTA17) and DOCK1 (BTA26). Among these genes PARK2, GUCY1A2, CPE and DOCK1 are related to dopaminergic system, memory formation, biosynthesis of peptide hormone and neurotransmitter and brain development, respectively.ConclusionsOur findings allowed us to identify nine genomic regions (SNP windows) associated with beef cattle temperament, measured by FS test. Within these windows, six promising candidate genes and their biological functions were identified. These results may contribute to a better comprehension into the genetic control of temperament expression in Nellore cattle.

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Section: Resultsmentioning

confidence: 99%

Genome-Wide Association Study between Single Nucleotide Polymorphisms and Flight Speed in Nellore Cattle

Valente¹,

Baldi²,

Sant’Anna³

et al. 2016

PLoS ONE

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“…However, the role and regulating mechanism of EMLO3 remains unclear compared with those of ELMO1 and ELMO2, which present unique and overlapping functions in different types of cancer [16,17,18,19,20,21,22,23]. In our current study, we observed high mRNA and protein levels of ELMO3 in CRC tissues and cell lines, which differs from that in many other cancers, including breast cancer, kidney cancer, hepatic cancer, etc.…”

Section: Discussionmentioning

confidence: 99%

“…The main protein structure of ELMOs is highly conserved and includes the ras GTPase-binding domain (RBD), ELMO inhibitory domain (EID), ELMO domain, PH domain, ELMO autoregulatory domain (EAD) and the extreme C-terminal proline-rich motifs [14,15]. Previous reports have revealed that ELMO1 and -2 are aberrantly expressed in a variety of human malignant tumors including primary gliomas [16,17], breast cancer [18], liver cancer [19], ovarian cancer [20,21], esophageal cancer [22] and rhabdomyosarcoma [23], and are closely related to the development, invasion and metastasis of tumors and play key roles in related signal regulating processes [16,20,24,25,26,27,28,29]. The ELMO1 and Dock proteins form a stable complex, which can be regulated by CXCR4 and directly interacts with the G protein α or β subunit to regulate Rac1 activation in response to chemoattractant G protein-coupled receptor activation.…”

Section: Introductionmentioning

confidence: 99%

Knockdown of ELMO3 Suppresses Growth, Invasion and Metastasis of Colorectal Cancer

Peng

Shen

et al. 2016

IJMS

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The engulfment and cell motility (ELMOs) family of proteins plays a crucial role in tumor cell migration and invasion. However, the function of ELMO3 is poorly defined. To elucidate its role in the development and progression of colorectal cancer (CRC), we examined the expression of ELMO3 in 45 cases of paired CRC tumor tissues and adjacent normal tissues. Furthermore, we assessed the effect of the knockdown of ELMO3 on cell proliferation, cell cycle, migration, invasion and F-actin polymerization in HCT116 cells. The result shows that the expression of ELMO3 in CRC tissues was significantly increased in comparison to the adjacent normal colorectal tissues. Moreover, this overexpression was associated with tumor size (p = 0.007), tumor differentiation (p = 0.001), depth of invasion (p = 0.009), lymph node metastasis (p = 0.003), distant metastasis (p = 0.013) and tumor, node, metastasis (TNM)-based classification (p = 0.000). In in vitro experiments, the silencing of ELMO3 inhibited cell proliferation, invasion, metastasis, and F-actin polymerization, and induced Gap 1 (G1) phase cell cycle arrest. Our study demonstrates that ELMO3 is involved in the processes of growth, invasion and metastasis of CRC, and could be used a potential molecular diagnostic tool or therapy target of CRC.

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“…Notably, we found that CFTR expression was significantly higher in the serous carcinoma and clear cell carcinoma as compared to the remaining carcinomas used in our study. Serous ovarian cancer is the most common histotype and accounts for more than half of epithelial ovarian cancer patients (17). Therefore, we selected the serous ovarian cancer cell lines for further study.…”

Section: Discussionmentioning

confidence: 99%

High level of CFTR expression is associated with tumor aggression and knockdown of CFTR suppresses proliferation of ovarian cancer in vitro and in vivo

Yong

et al. 2015

Oncology Reports

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The cystic fibrosis transmembrane conductance regulator (CFTR) belongs to the ATP-binding cassette (ABC) transporter family, members of which are involved in various types of cancer. The relationship between CFTR and ovarian cancer remains to be elucidated. The aim of the present study was to investigate the expression of CFTR in human ovarian cancer tissues and its clinical significance in the progression of ovarian cancer. The role of CFTR in the malignant invasion, migration and proliferation of ovarian cancer in vitro and in vivo was also investigated. Immunohistochemical staining analysis was performed to detect the expression of CFTR in 83 cases of human epithelial ovarian cancer specimens. Moreover, SKOV3 and A2780 stable cell lines containing shRNA gene specific for CFTR were established. Cell proliferation and motility were observed and compared with CFTR-RNAi cells. Tumorigenicity of CFTR-RNAi cells was investigated by tumor xenograft experiments conducted subcutaneously in nude mice. The expresssion of CFTR in ovarian cancer was significantly higher than that in benign ovarian tumor and normal ovaries (P<0.05). In ovarian cancer, CFTR expression was significantly associated with advanced FIGO stage, poor histopathological grade and serum Ca-125 (P<0.05). Furthermore, we observed that CFTR staining was stronger in the serous type as compared to the other types (P<0.05). Compared with the negative control, decreased cell invasion, migration, proliferation, adhesion and colony formation were observed in CFTR-RNAi cells in vitro. In vivo, tumorigenic abilities of CFTR-RNAi cells were significantly repressed compared with that of the control groups. CFTR overexpression may play an important role in the development and progression of ovarian cancer. Additionally, the downregulation of CFTR suppresses aggressive malignant biological behaviors of ovarian cancer cells in vitro and in vivo.

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Elmo1 Helps Dock180 to Regulate Rac1 Activity and Cell Migration of Ovarian Cancer

Abstract: Engulfment and cell motility 1 presents with synergetic action in helping Dock180 to activate Rac1 and promote cell motility, and thus promote untoward expansion and aggressiveness of SOC.

Cited by 21 publications

References 22 publications

Genome-Wide Association Study between Single Nucleotide Polymorphisms and Flight Speed in Nellore Cattle

Genome-Wide Association Study between Single Nucleotide Polymorphisms and Flight Speed in Nellore Cattle

Knockdown of ELMO3 Suppresses Growth, Invasion and Metastasis of Colorectal Cancer

High level of CFTR expression is associated with tumor aggression and knockdown of CFTR suppresses proliferation of ovarian cancer in vitro and in vivo

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