ILK over‐expression in human colon cancer progression correlates with activation of β‐catenin, down‐regulation of E‐cadherin and activation of the Akt–FKHR pathway

Bravou, Vasiliki; Klironomos, George; Papadaki, Eleni; Taraviras, Stavros; Varakis, John

doi:10.1002/path.1860

Cited by 87 publications

(96 citation statements)

References 39 publications

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“…10 In the in vivo studies using human cancer tissues, the expression of pFOXO1A has been correlated with an unfavorable outcome in acute myeloid leukemia 11 as well as tumor progression and metastasis in colon cancer. 12 In contrast, no significant correlation has been noted between pFOXO1A and any of the tumor characteristics of breast cancer.…”

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confidence: 84%

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Constitutive phosphorylation of the FOXO1A transcription factor as a prognostic variable in gastric cancer

Kim

Lee

et al. 2007

Modern Pathology

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Increased phosphorylation of FOXO1A, a FOXO transcription factor, has been implicated in several human cancers; however, it has not been studied in the gastric cancer to date. To determine the status of pFOXO1A expression in human gastric cancers and to determine its relationship with other tumor-associated proteins, we performed immunohistochemical staining on tissue array slides containing 272 human gastric carcinoma specimens. In non-neoplastic gastric mucosa, the expression of pFOXO1A was observed primarily in cells in the proliferative zone and in areas of intestinal metaplasia. In gastric carcinomas, the expression of pFOXO1A was observed in 230 (84.6%) out of 272 cases examined, and was positively correlated with the Ki-67-labeling index (P ¼ 0.026). The expression of pFOXO1A was higher in the early stages of pTNM (Po0.001), and was inversely correlated with the intestinal type by Lauren's classification (P ¼ 0.001), lymphatic invasion (P ¼ 0.017) and lymph node metastasis (Po0.001). Moreover, the expression of pFOXO1A was correlated with a longer patient survival (P ¼ 0.004). In addition, the expression of pFOXO1A was correlated with that of pAKT1 (Po0.001), PTEN (P ¼ 0.009), CDKN2A (P ¼ 0.012), APC (P ¼ 0.048), SMAD4 (Po0.001), CD82 (P ¼ 0.011), and BCL2 (P ¼ 0.011). In conclusion, our results showed that the expression of pFOXO1A is a frequent and early event in gastric tumorigenesis and that there is a significant correlation between pFOXO1A and better prognosis. Thus, our data suggest that the expression of pFOXO1A may serve as a valuable prognostic variable in gastric carcinoma and have significant implications for the development and application of targeted therapy.

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confidence: 84%

“…Our results disagree with other studies, which reported that the expression of pFOXO1A is associated with an unfavorable outcome in acute myeloid leukemia 11 or with the advanced stage of colon cancer. 12 Thus, the biological significance of the expression of pFOXO1A in the cancer appears to vary depending on the cancer cell type.…”

Section: Discussionmentioning

confidence: 99%

Constitutive phosphorylation of the FOXO1A transcription factor as a prognostic variable in gastric cancer

Kim

Lee

et al. 2007

Modern Pathology

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“…E-cadherin is one prominent adhesion molecule that forms the E-cadherin-catenin complex which plays a role in epithelial cell-cell adhesion and differentiation (38), in particular serving as a potent invasion/tumor suppressor of breast cancer (39). Previous studies indicated that the downregulation of E-cadherin was relevant to several pathways including the integrin-linked kinase (ILK) signaling pathway (40,41). The ILK signaling pathway was one prominent enrichment pathway in breast cancer, and may play an important role in hormonal cancer progression (42).…”

Section: Discussionmentioning

confidence: 99%

Differential proteomic analysis of pathway biomarkers in human breast cancer by integrated bioinformatics

Liu¹,

Jin²,

Shen³

2012

Oncology Letters

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Abstract. The aim of this study was to better understand the altered functional modules in breast cancer at pathway and network levels. An integrated bioinformatics analysis of differentially expressed proteins in human breast cancer was performed. Breast cancer protein profiles were constructed by data mining proteins in literature and public databases, including 1031 proteins with 153 secretory and 69 cell surface proteins. An experimental investigation was performed by two-dimensional electrophoresis, and 4 proteins were further validated by western blotting. Enriched bioinformatics functions were clustered. This study may be used as a reference in further studies to help identify the underlying biological interactions associated with breast cancer and discover potential cancer targets. IntroductionBreast cancer is the most common neoplasia in women and its pathogenesis is related to an acquired or inherited genetic disorder influenced by environmental, behavioral or reproductive factors (1). Cancer biomarker discovery is important for both cancer biology and clinical applications. These markers may come from DNA, RNA, miRNA or proteins (2), with proteins being the most significant (3).The development and improvement of biotechnologies has allowed researchers to perform high-throughput analyses of genomes, transcriptomes and proteomes in health and disease, and identify hundreds of potential biomarkers (4), offering the potential to discover diagnostic, prognostic or therapeutic targets. However, less than two dozen cancer biomarkers are currently approved by the Food and Drug Administration (FDA) (5), including only 9 protein biomarkers identified in the blood (6). Due to the lack of sensitivity and specificity of these known biomarkers (7), researchers continue to search for more significant targets. Proteomics is a promising approach for the discovery of cancer targets and biomarkers (8). The mapping of proteome profiles and differential proteomics has been widely performed in breast cancer to identify potential biomarkers (9). The identified proteins were reported to have potential clinical significance, and certain proteins may be used as potential diagnostic, prognostic or predictive biomarkers (10,11,12,13,14). However, due to the heterogeneity in the different studies, including experimental design, sample collection and classification and analytical method (15), these results lack good reproducibility and require further validation before they can be used in clinical detection and to explain the underlying mechanisms of breast cancer. In addition, few protein candidates were warranted to be specific to breast cancer, and were often differentially expressed in other cancer types (16). Hence, research encountered the challenge of how to decipher and use these individual results and bring them into clinical applications. In addition, an understanding of the underlying biological mechanisms of carcinogenesis and the altered molecular events in breast cancer at integrated pathway levels is necessary. Prot...

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“…A role for ILK in tumor progression is suggested by the observation that ILK expression correlates with high tumor grade and poor prognosis in a variety of human tumors (Chung et al, 1998;Graff et al, 2001;Marotta et al, 2001;Ahmed et al, 2003;Dai et al, 2003). In some cases, such as in human colon cancer, the upregulation of ILK protein levels corresponds to an increase in Akt phosphorylation (Bravou et al, 2006).…”

Section: Integrin-mediated Activation Of Pi3k Pathwaymentioning

confidence: 99%

The phosphatidyl inositol 3-kinase signaling network: implications for human breast cancer

2007

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ILK over‐expression in human colon cancer progression correlates with activation of β‐catenin, down‐regulation of E‐cadherin and activation of the Akt–FKHR pathway

Cited by 87 publications

References 39 publications

Constitutive phosphorylation of the FOXO1A transcription factor as a prognostic variable in gastric cancer

Constitutive phosphorylation of the FOXO1A transcription factor as a prognostic variable in gastric cancer

Differential proteomic analysis of pathway biomarkers in human breast cancer by integrated bioinformatics

The phosphatidyl inositol 3-kinase signaling network: implications for human breast cancer

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