P21-activated protein kinase 1 is overexpressed in gastric cancer and induces cancer metastasis

Li, Lianghui; Luo, Qi; Pan, Chao; Wu, Guoyang; Lu, Yuyan; Feng, Bo; Chen, Xuehua; Liu, Bingya

doi:10.3892/or.2012.1664

Cited by 18 publications

(35 citation statements)

References 20 publications

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“…The structures of PAK1 and PAK4 are different; the N-terminal regulatory region of PAK4 is fairly divergent from PAKs 1e3. For example, deletion of the PAK4 N-terminal regulatory domain (aa 291-591), mutation of its protein binding domain (H19L, H22L), and mutation of its activation loop (S474E) may lead to depression of the PAK4 catalytic domain [15]. Consistent with them, in our study, it was also shown that PAK4 expression level was higher than PAK1 in the same cancer tissue.…”

Section: Discussionsupporting

confidence: 88%

P21-activated kinase 1 and 4 were associated with colorectal cancer metastasis and infiltration

Song

Wang

Zheng

et al. 2015

Journal of Surgical Research

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Section: Discussionsupporting

confidence: 88%

P21-activated kinase 1 and 4 were associated with colorectal cancer metastasis and infiltration

Song

Wang

Zheng

et al. 2015

Journal of Surgical Research

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“…Taken together our findings suggest that gastrins stimulate cell proliferation and migration by activation of PAK1, which in turn activates multiple signaling pathways, including ERK, AKT, and ␤-catenin. Although PAK1 is overexpressed and hyperactivated in gastric and colon cancer (9,31), in vivo studies on the role of PAK1 in normal colon proliferation and its connection to gastrins have not been reported. The aim of this study was to investigate the role of PAK1 in the regulation by gastrin of the proliferation of colorectal mucosa in mouse models in which gastrin or PAK1 expression had been abrogated.…”

mentioning

confidence: 95%

p-21-Activated kinase 1 mediates gastrin-stimulated proliferation in the colorectal mucosa via multiple signaling pathways

Huynh

Yim

Chernoff

et al. 2013

American Journal of Physiology-Gastrointestinal and Liver Physi

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Gastrins, including amidated (Gamide) and glycine-extended (Ggly) forms, function as growth factors for the gastrointestinal mucosa. The p-21-activated kinase 1 (PAK1) plays important roles in growth factor signaling networks that control cell motility, proliferation, differentiation, and transformation. PAK1, activated by both Gamide and Ggly, mediates gastrin-stimulated proliferation and migration, and activation of β-catenin, in gastric epithelial cells. The aim of this study was to investigate the role of PAK1 in the regulation by gastrin of proliferation in the normal colorectal mucosa in vivo. Mucosal proliferation was measured in PAK1 knockout (PAK1 KO) mice by immunohistochemistry. The expression of phosphorylated and unphosphorylated forms of the signaling molecules PAK1, extracellular signal-regulated kinase (ERK), and protein kinase B (AKT), and the expression of β-catenin and its downstream targets c-Myc and cyclin D1, were measured in gastrin knockout (Gas KO) and PAK1 KO mice by Western blotting. The expression and activation of PAK1 are decreased in Gas KO mice, and these decreases are associated with reduced activation of ERK, AKT, and β-catenin. Proliferation in the colorectal mucosa of PAK1 KO mice is reduced, and the reduction is associated with reduced activation of ERK, AKT, and β-catenin. In compensation, antral gastrin mRNA and serum gastrin concentrations are increased in PAK1 KO mice. These results indicate that PAK1 mediates the stimulation of colorectal proliferation by gastrins via multiple signaling pathways involving activation of ERK, AKT, and β-catenin.

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“…Reports have shown that upregulation of UHRF1 is associated with lung cancer malignancy (Unoki et al, 2010) and with late TNM stage and lymph node metastasis in gallbladder cancer (Qin et al, 2014). Previous studies indicate that UHRF1 is regulated by E2F1 in breast and colorectal cancer; increased E2F1 can trigger tumor invasion and metastasis (Engelmann and Putzer, 2012;Kofunato et al, 2012;Li et al, 2012aLi et al, , 2012b. In the study, UHRF1 was one of the central nodes in the network with upregulation of both UHRF1 and E2F1, indicating that UHRF1 and E2F1 may be the key factors in the development of lung cancer in Xuanwei.…”

Section: Discussionmentioning

confidence: 95%

“…A high level of expression of PAK1 can promote the development of several cancers (Li et al, 2012a(Li et al, , 2012bQing et al, 2012;Lu et al, 2013). In NSCLC, PAK1 kinase promotes cell motility and invasiveness through CRK-II serine phosphorylation.…”

Section: Discussionmentioning

confidence: 98%

Gene expression profiling of lung adenocarcinoma in Xuanwei, China

Meng

et al. 2016

European Journal of Cancer Prevention

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The morbidity and mortality of lung cancer in Xuanwei, China, are the highest in the world. This study attempts to identify differentially expressed genes (DEGs) related to lung adenocarcinoma in Xuanwei. The expression profiles of eight paired lung adenocarcinoma tissues and corresponding nontumor tissues were acquired by microarrays. Functional annotations of DEGs were carried out by bioinformatics analysis. The results of the microarrays were further verified by real-time quantitative PCR (RTq-PCR). A total of 5290 genes were classified as DEGs in lung adenocarcinoma in Xuanwei; 3325 genes were upregulated and 1965 genes were downregulated, whereas the expression of the other 11 970 genes did not change. These DEGs are involved in a wide range of cancer-related processes, which include cell division, cell adhesion, cell proliferation, and DNA replication, and in many pathways such as the p53 signaling pathway, the MAPK pathway, the Jak-STAT signaling pathway, the hedgehog signaling pathway, and the non-small-cell lung cancer pathway. The tendency of changes in the expression of 12 selected DEGs (five downregulated genes, PIK3R1, RARB, HGF, MAPK11, and SESN1, and seven upregulated genes, PAK1, E2F1, CCNE1, EGF, CDC25A, PTTG1, and UHRF1) in RTq-PCR was consistent with the expression profiling data. Expression of PAK1 was significantly increased in the low differentiation group (P=0.031), whereas expression of HGF was significantly decreased in the low differentiation group (P=0.045). RARB and MAPK11 were significantly increased in the nonsmoker group (P=0.033 and 0.040, respectively). A large number of DEGs in lung adenocarcinoma in Xuanwei have been detected, which may enable us to understand the pathogenesis and lay an important foundation for the prevention and treatment of lung adenocarcinoma in Xuanwei.

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P21-activated protein kinase 1 is overexpressed in gastric cancer and induces cancer metastasis

Cited by 18 publications

References 20 publications

P21-activated kinase 1 and 4 were associated with colorectal cancer metastasis and infiltration

P21-activated kinase 1 and 4 were associated with colorectal cancer metastasis and infiltration

p-21-Activated kinase 1 mediates gastrin-stimulated proliferation in the colorectal mucosa via multiple signaling pathways

Gene expression profiling of lung adenocarcinoma in Xuanwei, China

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