Low expression of Rap1GAP is associated with epithelial-mesenchymal transition (EMT) and poor prognosis in gastric cancer

Yang, Ya; Jia, Zhang; Yan, Yan; Cai, Hui; Li, Min; Sun, Kai; Wang, Jizhao; Liu, Xu; Wang, Jiansheng; Duan, Xiaoyi

doi:10.18632/oncotarget.14074

Cited by 22 publications

(26 citation statements)

References 35 publications

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“…Decreased expression of Rap1GAP has been reported in pancreatic cancer ( 8 ), thyroid cancer ( 9 – 11 ), head and neck squamous cell carcinoma ( 12 ), melanoma ( 13 ), acute myeloid leukemia ( 14 ) and gastric cancer ( 20 ). Furthermore, the low expression of Rap1GAP in gastric cancer was significantly associated with TNM stage, lymph node metastasis, tumor diameter and poor OS, and therefore may be an independent prognostic factor of gastric cancer ( 20 ). These results strongly indicated that Rap1GAP may be used to identify individual patients with CRC who have a higher risk of recurrence and mortality and are therefore good candidates for receiving more aggressive treatment.…”

Section: Discussionmentioning

confidence: 99%

“…Furthermore, various in vivo and in vitro studies have suggested that Rap1GAP, as a type of tumor suppressor gene, serves an important role in tumor cell proliferation, invasion, migration and metastasis ( 10 , 13 , 16 – 18 ). In addition, decreased expression of Rap1GAP was associated with a poor prognosis in endometrial cancer and gastric cancer ( 19 , 20 ).…”

Section: Introductionmentioning

confidence: 99%

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The downregulation of Rap1 GTPase-activating protein is associated with a poor prognosis in colorectal cancer and may impact on tumor progression

Weili

Liu

et al. 2018

Oncol Lett

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Rap1 GTPase-activating protein (Rap1GAP) has been reported to serve an important role in various types of cancer by specific stimulation as a negative regulator of Rap1 activity. However, the role of Rap1GAP in colorectal cancer (CRC) has yet to be fully elucidated. The aim of the present study was to investigate the expression of Rap1GAP in CRC tissues and to elucidate its clinical significance. The expression of Rap1GAP, matrix metallopeptidase 9 (MMP-9) and E-cadherin in 227 CRC tissues and paired para-carcinoma tissues was detected by immunohistochemistry. Associations between Rap1GAP expression and clinicopathological characteristics, and between Rap1GAP expression and prognostic value (OS + DFS) in CRC were investigated. Furthermore, associations between Rap1GAP expression and MMP-9 expression, and between Rap1GAP expression and E-cadherin expression were also investigated. Rap1GAP expression was markedly downregulated in CRC tissues compared with para-carcinoma tissues. Decreased expression of Rap1GAP was significantly associated with depth of invasion, lymph node metastasis, advanced Tumor-Node-Metastasis stage and a poor prognosis in patients with CRC following surgery. Furthermore, univariate and multivariate analyses revealed that Rap1GAP was an independent poor prognostic factor for disease-free survival and overall survival. In addition, Rap1GAP expression was negatively associated with MMP-9 and positively associated with E-cadherin in 227 CRC samples. In brief, the results of the present study suggested that Rap1GAP may be involved in tumor progression in CRC and may serve as a potential target for prognostic prediction of patients with CRC.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

The downregulation of Rap1 GTPase-activating protein is associated with a poor prognosis in colorectal cancer and may impact on tumor progression

Weili

Liu

et al. 2018

Oncol Lett

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“…Further, EGFR and ADAM10 may be responsible for coupling moderate alcohol consumption to breast cancer by increasing EGFR signaling (Mill et al , 2009). RAP1GAP has been associated with prostate (Bailey et al , 2009) and gastric cancers (Yang et al , 2016). EGFR and YWHAB have been previously mapped to genetic network for alcohol-related phenotypes (Morozova et al , 2014).…”

Section: Discussionmentioning

confidence: 99%

Genetics of alcohol consumption in Drosophila melanogaster

Fochler

Morozova

Davis

et al. 2017

Genes Brain and Behavior

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Individual variation in alcohol consumption in human populations is determined by genetic, environmental, social and cultural factors. In contrast to humans, genetic contributions to complex behavioral phenotypes can be readily dissected in Drosophila, where both the genetic background and environment can be controlled and behaviors quantified through simple high-throughput assays. Here, we measured voluntary consumption of ethanol in ~3,000 individuals of each sex from an advanced intercross population derived from 37 lines of the Drosophila melanogaster Genetic Reference Panel. Extreme QTL mapping identified 385 differentially segregating allelic variants located in or near 291 genes at P < 10−8. The effects of single nucleotide polymorphisms associated with voluntary ethanol consumption are sex-specific, as found for other alcohol-related phenotypes. To assess causality we used RNAi knockdown or P[MiET1] mutants and their corresponding controls and functionally validated 86% of candidate genes in at least one sex. We constructed a genetic network comprised of 23 genes along with a separate trio and a pair of connected genes. Gene ontology analyses showed enrichment of developmental genes, including development of the nervous system. Furthermore, a network of human orthologs revealed enrichment for signal transduction processes, protein metabolism and developmental processes, including nervous system development. Our results show that the genetic architecture that underlies variation in voluntary ethanol consumption is sexually dimorphic and partially overlaps with genetic factors that control variation in feeding behavior and alcohol sensitivity. This integrative genetic architecture is rooted in evolutionarily conserved features that can be extrapolated to human genetic interaction networks.

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“…However, little is known about the regulatory role of Trop2 in TNBC. E-cadherin is a type of adhesion molecule that mainly exists in human and animal epithelium, and its main function is to maintain normal epithelial cell morphology and structural integrity (13)(14)(15). E-cadherin can regulate the close adhesion of epithelial cells and its downregulation is a key factor in WEI ZHAO 1* , XINGWANG KUAI 2* , XUEYI ZHOU 3 , LIZHOU JIA 2 , JINSONG WANG 1 , XIAOBING YANG 1 , ZHIDAN TIAN 1 , XIAOLEI WANG 1 , QIAN LV 1 , BIN WANG 1 , YOUCAI ZHAO 1 and WENBIN HUANG 1 epithelial neoplasm development (16).…”

Section: Introductionmentioning

confidence: 99%

Trop2 is a potential biomarker for the promotion of EMT in human breast cancer

et al. 2018

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Trop2 is considered to have an important function in tumor metastasis and the promotion of epithelial‑mesenchymal transition (EMT). E‑cadherin is a crucial factor in intercellular adhesion and EMT transformation. In the present study, we detected the expression of Trop2 and E‑cadherin in breast cancer (BC) to better define their prognostic value. The mRNA expression levels of these two genes in 20 cases of fresh BC tissues were detected by quantitative real‑time polymerase chain reaction (qRT‑PCR). We also detected the expression levels of these two genes by immunohistochemistry (IHC) in 312 BC tissues, and the correlations between the expression of these two genes and the clinicopathological characteristics in BC patients were analyzed. The mRNA and protein expression levels of the two genes in BC cell lines were studied by qRT‑PCR and western blotting. The results indicated that Trop2+/E‑cadherin‑ was expressed in BC tissues more than that in the matched adjacent tissues. The protein expression results obtained via IHC were similar to the mRNA expression results. Trop2+/E‑cadherin‑ that was expressed in BC was associated with lymph node status, metastasis, tumor‑node‑metastasis (TNM) stage, and ER‑/PR‑/HER2‑ expression. BC patients that expressed Trop2+/E‑cadherin‑ had poor overall survival rates. The results of Trop2 and E‑cadherin expression levels obtained in the BC cell lines were the same as those obtained in the BC tissues. Overall, Trop2 has a potential role in the promotion of EMT in BC and it could be considered as a therapeutic target in the future.

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Low expression of Rap1GAP is associated with epithelial-mesenchymal transition (EMT) and poor prognosis in gastric cancer

Cited by 22 publications

References 35 publications

The downregulation of Rap1 GTPase-activating protein is associated with a poor prognosis in colorectal cancer and may impact on tumor progression

The downregulation of Rap1 GTPase-activating protein is associated with a poor prognosis in colorectal cancer and may impact on tumor progression

Genetics of alcohol consumption in Drosophila melanogaster

Trop2 is a potential biomarker for the promotion of EMT in human breast cancer

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