PI3K/Akt-dependent phosphorylation of GSK3β and activation of RhoA regulate Wnt5a-induced gastric cancer cell migration

Liu, Jiaojing; Zhang, Yujie; Xu, Rui; Du, Jie; Hu, Zhenzhen; Yang, Lifen; Chen, Yongchang; Zhu, Yichao; Gu, Luo

doi:10.1016/j.cellsig.2012.10.012

Cited by 73 publications

(69 citation statements)

References 32 publications

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“…This interaction has been associated with cell proliferation in brain tumors such as malignant glioma. These studies suggest that EGFR activation and ECHS1 expression promotes tumor growth, especially through the non-canonical Wnt signaling-mediated activation of β-catenin [11]. In this study, we found that ECHS1 knockdown suppressed GSK3β phosphorylation.…”

Section: Discussionsupporting

confidence: 57%

“…Cell migration is an important property of malignant cancers. Previous studies have established the key roles of the PI3K-PKB signaling and GSK3β in the regulation of cell migration [11,30,31]. Transducer of ErbB-2.1-mediated decrease of PKB and GSK3β phosphorylation in MKN28 and AGS cells inhibits the proliferation and migration of both gastric cancer cell lines [30].…”

Section: Discussionmentioning

confidence: 97%

“…It has been implicated in many cancers due to its essential role in cell proliferation regulation, cell cycle progression and cell survival [6][7][8]. The phosphorylation of glycogen synthase kinase 3 (GSK3) by PKB regulates cell differentiation, proliferation and migration, and is also involved in tumorigenesis [9][10][11]. Reducing PKB activation is a target for gastric cancer treatment, and many therapeutic interventions targeting PKB have been developed for clinical use [12].…”

Section: Introductionmentioning

confidence: 99%

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Attenuation of enoyl coenzyme A hydratase short chain 1 expression in gastric cancer cells inhibits cell proliferation and migration in vitro

Zhu

Gao

Yichen

et al. 2014

Cellular and Molecular Biology Letters

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Enoyl coenzyme A hydratase short chain 1 (ECHS1) is an important part of the mitochondrial fatty acid β-oxidation pathway. Altered ECHS1 expression has been implicated in cancer cell proliferation. This study assessed ECHS1 expression in human gastric cancer cell lines and investigated the effects of ECHS1 knockdown on gastric cancer cell proliferation and migration. The human gastric cancer cell lines SGC-7901, BGC-823 and MKN-28, and the immortalized human gastric epithelial mucosa GES-1 cell line were analyzed for ECHS1 protein levels using western blot. The effectiveness of ECHS1-RNA interference was also determined using western blot. Proliferation and migration of the siECHS1 cells were respectively measured with the CCK-8 and transwell assays. Phosphorylation of PKB and GSK3β was assessed using western blot. ECHS1 protein levels were significantly higher in poorly differentiated cells than in well-differentiated cells and immortalized gastric epithelial mucosa cells. Stable expression of ECHS1 shRNA was associated with an over 41% reduction in the ECHS1 protein levels of siECHS1 cells. Constitutive knockdown of the ECHS1 gene in siECHS1 cells was associated with significantly inhibited cell proliferation and migration. We also observed decreased levels of PKB and GSK3β phosphorylation in siECHS1 cells. ECHS1 expression is increased in human gastric cancer cells. Increased ECHS1 expression activates PKB and GSK3β by inducing the phosphorylation of the two kinases. ECHS1 may play important roles in gastric cancer cell proliferation and migration through PKB- and GSK3β-related signaling pathways.

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Section: Discussionsupporting

confidence: 57%

Section: Discussionmentioning

confidence: 97%

Section: Introductionmentioning

confidence: 99%

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Attenuation of enoyl coenzyme A hydratase short chain 1 expression in gastric cancer cells inhibits cell proliferation and migration in vitro

Zhu

Gao

Yichen

et al. 2014

Cellular and Molecular Biology Letters

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“…Recently, it has been reported that RhoA activation is required for Wnt5a/PI3K/Akt/glycogen synthase kinase 3b activity and that Wnt5a/PI3K/Akt/glycogen synthase kinase 3b/RhoA signaling may contribute to cell migration [36]. Our previous study demonstrated that GKN1 inhibits gastric cancer migration and invasion through suppression of reactive oxygen species and the PI3K/Akt pathway [12].…”

Section: Discussionmentioning

confidence: 94%

Gastrokine 1 inhibits gastric cancer cell migration and invasion by downregulating RhoA expression

et al. 2016

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Background We investigated whether GKN1, a gastric tumor suppressor, contributes to the progression of gastric cancer by regulating RhoA expression. Methods We analyzed the expression of GKN1, RhoA, miR-185, and miR-34a in 35 gastric cancer tissues, and compared their expression with T category and TNM stage. Cell migration and invasion, as well as the expression of epithelial-to-mesenchymal transition (EMT)-related proteins, were assessed in GKN1-and RhoA small interfering RNA (siRhoA)-transfected and recombinant-GKN1-treated AGS and MKN1 gastric cancer cells. Results Expression of RhoA protein and messenger RNA (mRNA) was increased in 15 (42.9 %) and 17 (48.6 %) of 35 gastric cancer tissues respectively, and was associated with higher T category and TNM stage. GKN1 expression was significantly decreased in 27 gastric cancers (77.1 %) with a higher T category, and was inversely correlated with RhoA mRNA expression. In AGS and MKN1 cells, GKN1 expression increased miR-185 and miR-34a expression and reduced RhoA mRNA and protein expression. A positive relationship between GKN1 and miR-34a and miR-185 expression and an inverse relationship between miR-34a and RhoA expression were observed in gastric cancer tissues. Cell migration and invasiveness were markedly decreased in GKN1-and siRhoA-transfected cells. GKN1 expression and silencing of RhoA decreased the expression of the proteins Snail, Slug, and vimentin. Furthermore, miR-185 and miR-34a silencing in MKN1 cells transfected with GKN1 stimulated cell migration and invasion, and increased the expression of EMT-related proteins. Conclusion Our data suggest that GKN1 may inhibit gastric cancer cell migration and invasion by downregulating RhoA expression in a miR-185-and miR-34a-dependent manner.

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“…Gastric cancer is one of the most frequently occurring malignancies (Liu et al, 2013) and the second leading Chun-Yu Zhu 1,2 , Yan-Ping Lv 3 , Deng-Feng Yan 2 , Fu-Lian Gao 1 * cause of cancer mortality in the world (Zhang and Fan, 2007;Li et al, 2011). Surgery and chemotherapy are the major treatment modalities for this cancer and significantly improved overall survival.…”

Section: Introductionmentioning

confidence: 99%

Knockdown of MDR1 Increases the Sensitivity to Adriamycin in Drug Resistant Gastric Cancer Cells

Zhu

Lv²,

Yan³

et al. 2013

Asian Pacific Journal of Cancer Prevention

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Gastric cancer is one of the most frequently occurring malignancies in the world. Development of multiple drug resistance (MDR) to chemotherapy is known as the major cause of treatment failure for gastric cancer. Multiple drug resistance 1/P-glycoprotein (MDR1/p-gp) contributes to drug resistance via ATP-dependent drug efflux pumps and is overexpressed in many solid tumors including gastric cancer. To investigate the role of MDR1 knockdown on drug resistance reversal, we knocked down MDR1 expression using shRNA in drug resistant gastric cancer cells and examined the consequences with regard to adriamycin (ADR) accumulation and drugsensitivity. Two shRNAs efficiently inhibited mRNA and protein expression of MDR1 in SGC7901-MDR1 cells. MDR1 knockdown obviously decreased the ADR accumulation in cells and increased the sensitivity to ADR treatment. Together, our results revealed a crucial role of MDR1 in drug resistance and confirmed that MDR1 knockdown could reverse this phenotype in gastric cancer cells.

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PI3K/Akt-dependent phosphorylation of GSK3β and activation of RhoA regulate Wnt5a-induced gastric cancer cell migration

Cited by 73 publications

References 32 publications

Attenuation of enoyl coenzyme A hydratase short chain 1 expression in gastric cancer cells inhibits cell proliferation and migration in vitro

Attenuation of enoyl coenzyme A hydratase short chain 1 expression in gastric cancer cells inhibits cell proliferation and migration in vitro

Gastrokine 1 inhibits gastric cancer cell migration and invasion by downregulating RhoA expression

Knockdown of MDR1 Increases the Sensitivity to Adriamycin in Drug Resistant Gastric Cancer Cells

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