Wnt Pathway in Osteosarcoma, from Oncogenic to Therapeutic

Cai, Yu-Dong; Cai, Tiange; Chen, Yan

doi:10.1002/jcb.24708

Cited by 86 publications

(78 citation statements)

References 51 publications

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“…GO terms related to translation (e.g., cytoplasmic translation) were also enriched in OS genes. In line with previous studies, several pathways, such as mTOR signaling pathway (ranked 5th) (29,30), Hippo signaling pathway (ranked 9th) (31), PI3K-Akt signaling pathway (ranked 10th) (30,32), MAPK signaling pathway (ranked 11th) (33), Wnt signaling pathway (ranked 22nd) (34,35), p53 signaling pathway (ranked 24th) (36–38), and TGF-β signaling pathway (ranked 27th) (38,39), were enriched in OS genes. In addition, several cancer-related pathways were identified, such as Pathways in cancer, Proteoglycans in cancer, central carbon metabolism in cancer, and transcriptional misregulation in cancer.…”

Section: Resultssupporting

confidence: 88%

Analyzing the disease module associated with osteosarcoma via a network‑ and pathway‑based approach

Zhang

2018

Exp Ther Med

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Osteosarcoma is the most common type of primary malignant bone tumor observed in children and adolescents. The aim of the present study was to identify an osteosarcoma-related gene module (OSM) by looking for a dense module following the integration of signals from genome-wide association studies (GWAS) into the human protein-protein interaction (PPI) network. A dataset of somatic mutations in osteosarcoma was obtained from the dbGaP database and their testing P-values were incorporated into the PPI network from a recent study using the dmGWAS bioconductor package. An OSM containing 201 genes (OS genes) and 268 interactions, which were closely associated with immune response, intracellular signal transduction and cell activity was identified. Topological analysis of the OSM identified 11 genes, including APP, APPBP2, ATXN1, HSP90B1, IKZF1, KRTAP10-1, PAK1, PDPK1, SMAD4, SUZ12 and TP53 as potential diagnostic biomarkers for osteosarcoma. The overall survival analysis of osteosarcoma for those 11 genes based on a dataset from the Cancer Genome Atlas, identified APP, HSP90B1, SUZ12 and IKZF1 as osteosarcoma survival-related genes. The results of the present study should be helpful in understanding the diagnosis and treatment of osteosarcoma and its underlying mechanisms. In addition, the methodology used in the present study may be suitable for the analysis of other types of disease.

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Section: Resultssupporting

confidence: 88%

Analyzing the disease module associated with osteosarcoma via a network‑ and pathway‑based approach

Zhang

2018

Exp Ther Med

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“…The role of Wnt signaling in sarcoma biology remains controversial, with some studies suggesting an oncogenic role for this pathway, and other studies supporting an anti-tumorigenic role [26, 27]. Our work directly addresses this controversy.…”

Section: Discussionmentioning

confidence: 88%

A monoclonal antibody against the Wnt signaling inhibitor dickkopf-1 inhibits osteosarcoma metastasis in a preclinical model

et al. 2016

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The outcome of patients with metastatic osteosarcoma has not improved since the introduction of chemotherapy in the 1970s. Development of therapies targeting the metastatic cascade is a tremendous unmet medical need. The Wnt signaling pathway has been the focus of intense investigation in osteosarcoma because of its role in normal bone development. Although the role of Wnt signaling in the pathogenesis of osteosarcoma is controversial, there are several reports of dickkopf-1 (DKK-1), a Wnt signaling antagonist, possibly playing a pro-tumorigenic role. In this work we investigated the effect of anti-DKK-1 antibodies on the growth and metastasis of patient-derived osteosarcoma xenografts. We were able to detect human DKK-1 in the blood of tumor-bearing mice and found a correlation between DKK-1 level and tumor proliferation. Treatment with the anti-DKK-1 antibody, BHQ880, slowed the growth of orthotopically implanted patient-derived osteosarcoma xenografts and inhibited metastasis. This effect was correlated with increased nuclear beta-catenin staining and increased expression of the bone differentiation marker osteopontin. These findings suggest that Wnt signaling is anti-tumorigenic in osteosarcoma, and support the targeting of DKK-1 as an anti-metastatic strategy for patients with osteosarcoma.

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“…Other key pathways that regulate cell adhesion, migration, proliferation and survival were downregulated, and have been associated with numerous tumors, including breast and thyroid carcinoma (26). The p53 signaling pathway was demonstrated to serve a pivotal role by forming a complex with its target genes to suppress tumorigenesis (27), and the Wnt signaling pathway, which is a complex network of protein-protein interactions and a major pathway involved in cancer development and embryogenesis, have been reported to be abnormally regulated in a variety of tumors (28)(29)(30)(31). Amongst the pathways associated with the differentially expressed genes in the present study, 6 genes identified to have previously been directly associated with colorectal cancer: T-cell-specific transcription factor 1 (TCF7) (32), cyclin D1 (CCND1) (33), tyrosin-protein kinase met (MET) (34), lymphoid enhancer binding factor 1 (LEF1) (35), axin 2 (AXIN2) (36) and MYC (37).…”

Section: Discussionmentioning

confidence: 99%

Gene expression profile comparison between colorectal cancer and adjacent normal tissues

Yang

Mao

et al. 2017

Oncol Lett

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Abstract. The present study aimed to compare gene expression profiles between colorectal cancer and adjacent normal tissues, and to perform a preliminarily analysis of the key genes and underlying molecular mechanisms implicated in colorectal cancer development. Gene expression microarray chips were used to screen genes that were differently expressed between colorectal cancer and adjacent normal tissues. Approximately 1,183 genes were differentially expressed in cancer tissues compared with adjacent normal tissues (P≤0.05; fold difference, >2.0), of which 570 genes were upregulated and 613 genes were downregulated. In total, 6 upregulated genes, including keratin 23, collagen type X α1, collagen type XI α1, cell migration-inducing hyaluronan-binding protein, transforming growth factor-β1 and V-Myc avian myelocytomatosis viral oncogene homolog, and 2 downregulated genes, including channel α subunit 7 and EPH receptor A7, were selected and validated using reverse transcription-quantitative polymerase chain reaction, which exhibited results that were consistent with the microarray analysis. These 1,183 differentially expressed genes were further classified into 71 groups based on their functions using gene ontology and pathway analyses. Kyoto Encyclopedia of Genes and Genomes analysis of these upregulated or downregulated genes suggested that 23 signaling pathways were involved. The present study preliminarily screened for and identified key genes and signaling pathways that may be closely associated with colorectal cancer development. However, subsequent gene function studies are required to verify these findings. IntroductionColorectal cancer (CRC) is a common gastrointestinal cancer and its global incidence is outranked only by gastric and esophageal cancers (1). There were ~14.1 million new cases of cancer globally in 2012, of which CRC accounted for 1.4 million and in China, was surpassed only by lung and breast cancers (2). In China, the incidence of CRC and its mortality rate have been ranked third and fourth, respectively among malignant tumors (3). Studies have demonstrated that China's annual incidence of CRC increases twice as fast compared with the global average (3,4). In Shanghai, Beijing and Guangzhou, the incidence of colorectal cancer is 40/100,000 individuals (5); and a previous CRC survey program in Wuhan, Hubei province has reported a high incidence of 90/100,000 individuals, which is twice that of the national average (6). According to the National Bowel Cancer Screening Programme, whose aim was to reduce the incidence of symptomatic CRC, the majority of patients present with symptoms to their general practitioner (7-9). An isolated symptom may be associated with CRC, but typically symptoms were observed in clusters. In total ≥1 high-risk symptoms are seen in ~85% of patients with CRC, who were referred to secondary care (10). However, symptoms for disease may be biased to a certain extent by 'selection phenomena', and this is the case to CRC (11). When performing diagnostic research in second...

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Wnt Pathway in Osteosarcoma, from Oncogenic to Therapeutic

Cited by 86 publications

References 51 publications

Analyzing the disease module associated with osteosarcoma via a network‑ and pathway‑based approach

Analyzing the disease module associated with osteosarcoma via a network‑ and pathway‑based approach

A monoclonal antibody against the Wnt signaling inhibitor dickkopf-1 inhibits osteosarcoma metastasis in a preclinical model

Gene expression profile comparison between colorectal cancer and adjacent normal tissues

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