Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P31749 (AKT)
 22,954 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A significant challenge in the post-genomic era is how to prioritize differentially expressed and uncharacterized novel genes found in hepatocellular carcinoma (HCC) microarray profiling. One such category is cell cycle regulated genes that have only evolved in higher organisms but not in lower eukaryotic cells. Characterization of these genes may reveal some novel human cancer-specific abnormalities. A novel transcript, FLJ10540 was identified. FLJ10540 is overexpressed in HCC as examined by quantitative reverse transcription-polymerase chain reaction and immunohistochemistry. The patients with higher FLJ10540 expression had a poor survival than those with lower FLJ10540 expression. Functional characterization indicates that FLJ10540 displays a number of characteristics associated with an oncogene, including anchorage-independent growth, enhanced cell growth at low serum levels and induction of tumorigenesis in nude mice. FLJ10540-elicited cell transformation is mediated by activation of the phosphatidylinositol 3'-kinase (PI3K)/AKT pathway. Moreover, FLJ10540 forms a complex with PI3K and can activate PI3K activity, which provides a mechanistic basis for FLJ10540-mediated oncogenesis. Together, using a combination of bioinformatics searches and empirical data, we have identified a novel oncogene, FLJ10540, which is conserved only in higher organisms. The finding raises the possibility that FLJ10540 is a potential new therapeutic target for HCC treatment. These findings may contribute to the development of new therapeutic strategies that are able to block the PI3K/AKT pathway in cancer cells.
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PMID:FLJ10540-elicited cell transformation is through the activation of PI3-kinase/AKT pathway. 1723 22

Tumor invasion and metastasis are the primary causes of cancer patient mortality, underscoring the need for identification of novel genes and signaling pathways that mediate these prognosis-determining phenomena. To identify and characterize novel lung adenocarcinoma genes associated with lung cancer progression, we created a bioinformatics-based approach that focuses on human cell-cycle-regulated genes that have evolved only in higher organisms but not in lower eukaryotic cells. In siRNA experiments in lung cancer cells, FLJ10540 was identified as one of several novel targets involved in cell migration and invasion. Here, we demonstrate that PI3K inhibition affects FLJ10540-mediated cell migration and invasion and further, that FLJ10540 knockdown ablates AKT-Ser(473) phosphorylation. Taken together, these findings indicate that the FLJ10540/PI3K/AKT pathway may harbor new therapeutic targets for treating invasive lung adenocarcinoma.
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PMID:Using siRNA to uncover novel oncogenic signaling pathways. 2021 55

CEP55 was initially described as a centrosome- and midbody-associated protein and a key mediator of cytokinesis. More recently, it has been implicated in PI3K/AKT pathway activation via an interaction with the catalytic subunit of PI3K. However, its role in embryonic development is unknown. Here we describe a cep55 nonsense mutant zebrafish with which we can study the in vivo physiologic role of Cep55. Homozygous mutants underwent extensive apoptosis by 24 hours postfertilization (hpf) concomitant with cell cycle defects, and heterozygous carriers were indistinguishable from their wild-type siblings. A similar phenotype was also observed in zebrafish injected with a cep55 morpholino, suggesting the mutant is a cep55 loss-of-function model. Further analysis revealed that Akt was destabilized in the homozygous mutants, which partially phenocopied Akt1 and Akt2 knockdown. Expression of either constitutively activated PIK3CA or AKT1 could partially rescue the homozygous mutants. Consistent with a role for Cep55 in regulation of Akt stability, treatment with proteasome inhibitor, MG132, partially rescued the homozygous mutants. Taken together, these results provide the first description of Cep55 in development and underline the importance of Cep55 in the regulation of Pi3k/Akt pathway and in particular Akt stability.
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PMID:Cep55 regulates embryonic growth and development by promoting Akt stability in zebrafish. 2566 21

CEP55 was initially identified as a pivotal component of abscission, the final stage of cytokinesis, serving to regulate the physical separation of two daughter cells. Over the past 10 years, several studies have illuminated additional roles for CEP55 including regulating the PI3K/AKT pathway and midbody fate. Concurrently, CEP55 has been studied in the context of cancers including those of the breast, lung, colon and liver. CEP55 overexpression has been found to significantly correlate with tumor stage, aggressiveness, metastasis and poor prognosis across multiple tumor types and therefore has been included as part of several prognostic 'gene signatures' for cancer. Here by discussing in depth the functions of CEP55 across different effector pathways, and also its roles as a biomarker and driver of tumorigenesis, we assemble an exhaustive review, thus commemorating a decade of research on CEP55.
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PMID:Beyond cytokinesis: the emerging roles of CEP55 in tumorigenesis. 2591 44

Several genes and pathways associated with oral squamous cell carcinoma (OSCC) are significant in terms of early detection and prognosis. The objective of this literature review is to evaluate the current research on molecular pathways and genes involved in oral cancer. Articles on the genes involved in oral cancer pathways were evaluated to identify potential biomarkers that can predict survival. In total, 36 articles were retrieved from internet databases, including EBSCO Host, Google Scholar, PubMed, and Science Direct, using the keywords "biomarker of oral cancer," "pathways of oral cancer," "genes involved in oral cancer," and "oral cancer pathways." A total of 36 studies related to OSCC were chosen. Most of the studies used cell lines, while others used archival tissues, few studies followed up the cases. Three major interlinked pathways found were the nuclear factor kappa B (NF-kB), PI3K-AKT, and Wnt pathways. The commonly mutated genes were cyclin D1 (CCND1), Rb, p53, FLJ10540, and TC21. The NF-kB, PI3K-AKT, and Wnt pathways are most frequently involved in the molecular pathogenesis of oral cancer. However, the CCND1, Rb, p53, FLJ10540, and TC21 genes were found to be more accurate in determining patients' overall survival. Polymerase chain reaction, immunohistochemistry, and immunoblotting were the commonly used detection methods.
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PMID:Molecular pathways of oral cancer that predict prognosis and survival: A systematic review. 3076 50

Centrosomal Protein 55 (Cep55), also known as c10orf3 and FLJ10540, was initially discovered as a major player in abscission, the final stage of cytokinesis. Subsequent studies have described its role in regulating the PI3K/AKT pathway, increasing cancer cell stemness, and promoting tumor formation. Clinically, Cep55 has been found to be overexpressed in many cancer types. Cep55 overexpression has been notably associated with tumor stage, tumor aggressiveness, poor prognosis, and metastasis. The present review discusses the role of Cep55 as a crucial biomarker and model in tumorigenesis.
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PMID:Centrosomal protein 55: A new paradigm in tumorigenesis. 3264 45