Periostin activates integrin α5β1 through a PI3K/AKT-dependent pathway in invasion of cholangiocarcinoma

Utispan, Kusumawadee; Sonongbua, Jumaporn; Thuwajit, Peti; Chau-in, Siri; Pairojkul, Chawalit; Wongkham, Sopit; Thuwajit, Chanitra

doi:10.3892/ijo.2012.1530

Cited by 99 publications

(94 citation statements)

References 46 publications

(61 reference statements)

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“…29 The PI3K/Akt pathway plays a fundamental role in the development of gastric cancer, 30 and accumulating evidences have indicated that periostin can promote cancer cell growth and inhibit apoptosis by activating the PI3K/Akt pathway in human cancers, such as colon cancer, cholangiocarcinoma, prostate cancer, and non-small-cell lung cancer (NSCLC). 8,[31][32][33] Conversely, periostin plays a tumor-suppressor role in bladder cancer by repressing its activity. 32 Moreover, periostin has also been revealed to exhibit a biphasic effect on Akt activity in pancreatic cancer cells with an increase of Akt activity at the high concentration but a decrease at the low concentration.…”

Section: Discussionmentioning

confidence: 96%

Epithelial cell-derived periostin functions as a tumor suppressor in gastric cancer through stabilizing p53 and E-cadherin proteins via the Rb/E2F1/p14ARF/Mdm2 signaling pathway

et al. 2014

Cell Cycle

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Periostin is usually considered as an oncogene in diverse human cancers, including breast, prostate, colon, esophagus, and pancreas cancers, whereas it acts as a tumor suppressor in bladder cancer. In gastric cancer, it has been demonstrated that periglandular periostin expression is decreased whereas stromal periostin expression is significantly increased as compared with normal gastric tissues. Moreover, periostin produced by stromal myofibroblasts markedly promotes gastric cancer cell growth. These observations suggest that periostin derived from different types of cells may play distinct biological roles in gastric tumorigenesis. The aim of this study was to explore the biological functions and related molecular mechanisms of epithelial cell-derived periostin in gastric cancer. Our data showed that periglandular periostin was significantly down-regulated in gastric cancer tissues as compared with matched normal gastric mucosa. In addition, its expression in metastatic lymph nodes was significantly lower than that in their primary cancer tissues. Our data also demonstrated that periglandular periostin expression was negatively associated with tumor stage. More importantly, restoration of periostin expression in gastric cancer cells dramatically suppressed cell growth and invasiveness. Elucidation of the mechanisms involved revealed that periostin restoration enhanced Rb phosphorylation and sequentially activated the transcription of E2F1 target gene p14(ARF), leading to Mdm2 inactivation and the stabilization of p53 and E-cadherin proteins. Strikingly, these effects of periostin were abolished upon Rb deletion. Collectively, we have for the first time demonstrated that epithelial cell-derived periostin exerts tumor-suppressor activities in gastric cancer through stabilizing p53 and E-cadherin proteins via the Rb/E2F1/p14(ARF)/Mdm2 signaling pathway.

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Section: Discussionmentioning

confidence: 96%

Epithelial cell-derived periostin functions as a tumor suppressor in gastric cancer through stabilizing p53 and E-cadherin proteins via the Rb/E2F1/p14ARF/Mdm2 signaling pathway

et al. 2014

Cell Cycle

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“…Intriguingly, it has been shown that reduced Atf3, Egr1, Itgb1, and Akip1 levels leads to Akt inactivation (20 -23), whereas up-regulation of Postn and Rfxp1 (24,25) or down-regulation of Egln3 promotes Akt activation (26) (Fig. 4G).…”

Section: Generation Of Mir-223 Transgenic Mousementioning

confidence: 91%

Overexpression of miR-223 Tips the Balance of Pro- and Anti-hypertrophic Signaling Cascades toward Physiologic Cardiac Hypertrophy

Yang

Wang

et al. 2016

Journal of Biological Chemistry

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MicroRNAs (miRNAs) have been extensively examined in pathological cardiac hypertrophy. However, few studies focused on profiling the miRNA alterations in physiological hypertrophic hearts. In this study we generated a transgenic mouse model with cardiac-specific overexpression of miR-223. Our results showed that elevation of miR-223 caused physiological cardiac hypertrophy with enhanced cardiac function but no fibrosis. Using the next generation RNA sequencing, we observed that most of dys-regulated genes (e.g. Atf3/5, Egr1/3, Sfrp2, Itgb1, Ndrg4, Akip1, Postn, Rxfp1, and Egln3) in miR-223-transgenic hearts were associated with cell growth, but they were not directly targeted by miR-223. Interestingly, these dysregulated genes are known to regulate the Akt signaling pathway. We further identified that miR-223 directly interacted with 3-UTRs of FBXW7 and Acvr2a, two negative regulators of the Akt signaling. However, we also validated that miR-223 directly inhibited the expression of IGF-1R and ␤1-integrin, two positive regulators of the Akt signaling. Lastly, Western blotting did reveal that Akt was activated in miR-223-overexpressing hearts. Adenovirus-mediated overexpression of miR-223 in neonatal rat cardiomyocytes induced cell hypertrophy, which was blocked by the addition of MK2206, a specific inhibitor of Akt. Taken together, these data represent the first piece of work showing that miR-223 tips the balance of promotion and inactivation of Akt signaling cascades toward activation of Akt, a key regulator of physiological cardiac hypertrophy. Thus, our study suggests that the ultimate phenotype outcome of a miRNA may be decided by the secondary net effects of the whole target network rather than by several primary direct targets in an organ/tissue.Cardiac hypertrophy is an adaptive mechanism of cardiomyocytes to different forms of injury or stress, such as myocardial infarction, hypertension, and valve disease (pathological) or chronic exercise training (physiological) (1). Both pathological and physiological cardiac hypertrophy types are featured with increased myocyte size, but they have distinct molecular and functional phenotypes (2). Pathological cardiac hypertrophy is often associated with interstitial fibrosis and increased myocyte necrosis/apoptosis, leading to cardiac dysfunction (1, 2). By contrast, exercise training-induced physiological cardiac hypertrophy is characterized by overall normal cardiac structure and function, presenting an adaptive beneficial response (1, 2). Indeed, exercise training is clinically recommended as the most effective non-pharmacological intervention to reduce cardiovascular disease (2). Thus, elucidating the molecular mechanisms underlying physiological cardiac hypertrophy would help us identify novel therapies for the treatment of cardiovascular disease.MicroRNAs (miRNAs) 3 are small, endogenous, non-coding RNAs of ϳ22 to 26 nucleotides in length that function primarily as post-transcriptional regulators (3). Importantly, a single miRNA does not only regulate one gene ...

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“…However, liver weight and TG content were significantly reduced in Postn-heterozygous mice and MPHs (Supplemental Figure 14), which suggests that fatty acids might also be involved in regulation of periostin expression in obesity-associated hepatosteatosis. It has been reported that periostin exerts its biological functions through several signaling pathways in the development of human cancers, including PI3K/AKT and Wnt/β-catenin (12,34,35). However, AKT phosphorylation was not altered in livers of mice overexpressing periostin.…”

Section: Disruption Of Postn Improves Hepatosteatosis In Obese Micementioning

confidence: 93%

Periostin promotes liver steatosis and hypertriglyceridemia through downregulation of PPARα

Lu¹,

Liu²,

Jiao³

et al. 2014

J. Clin. Invest.

114

128

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Periostin neutralizing Ab. The hybridoma cell lines secreting mouse mAb against mouse periostin were generated by Abmart Co., according to the standard hybridoma technique (72). The mouse mAbs were purified by Protein A affinity chromatograph. mAb purity was confirmed by HPLC. The concentrations of the obtained mAbs were measured by Mouse IgG ELISA Quantitation kit (Bethyl Laboratories), following the manufacturer's instructions. The kinetic parameters of the mAbs were determined using a Biacore T100 instrument (Biacore AB). Purified Ab was diluted in saline and injected at a dose of 5 mg/kg into db/db mice for 2 weeks.Statistics. All values are shown as mean ± SEM. Statistical differences were determined by 2-way ANOVA with Bonferroni-adjusted post-test or by 2-tailed Student's t test. A P value less than 0.05 was considered significant.

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Periostin activates integrin α5β1 through a PI3K/AKT-dependent pathway in invasion of cholangiocarcinoma

Cited by 99 publications

References 46 publications

Epithelial cell-derived periostin functions as a tumor suppressor in gastric cancer through stabilizing p53 and E-cadherin proteins via the Rb/E2F1/p14ARF/Mdm2 signaling pathway

Epithelial cell-derived periostin functions as a tumor suppressor in gastric cancer through stabilizing p53 and E-cadherin proteins via the Rb/E2F1/p14ARF/Mdm2 signaling pathway

Overexpression of miR-223 Tips the Balance of Pro- and Anti-hypertrophic Signaling Cascades toward Physiologic Cardiac Hypertrophy

Periostin promotes liver steatosis and hypertriglyceridemia through downregulation of PPARα

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