Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0178874 (tumor progression)
 40,807 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The S100 gene family, which is composed of at least 24 members carrying the Ca2+ binding EF-hand motif, has been implicated in both intracellular and extracellular functions, including enzyme activities, immune responses, cytoskeleton dynamics, Ca2+ homeostasis, cell growth and cell differentiation. Altered S100 protein levels are associated with a broad range of diseases, including cardiomyopathy, inflammatory and immune disorders, neurodegenerative disorders and cancer. Although the precise role of S100 protein in carcinogenesis is poorly understood, it seems that formation of homo- and hetero-dimers, binding of Ca2+ and interaction with effector molecules are essential for the development and progression of many cancers. Several studies have suggested that S100 proteins promote cancer progression and metastasis through cell survival and apoptosis pathways. In animal models of bladder cancer, several S100 proteins are differentially expressed in bladder tumors relative to normal urothelium. In human bladder cancer, overexpression of S100A4, S100A8 or S100A11 are associated with stage progression, invasion, metastasis and poor survival. This review summarizes these findings and evaluates their implications for human bladder cancer management.
 ...
PMID:The S100 proteins for screening and prognostic grading of bladder cancer. 1752 80

Multiple reports have focused on S100A4's role in cancer progression, specifically its ability to enhance metastasis. However, recent studies have linked S100A4 to several diseases besides cancer, including kidney fibrosis, cirrhosis, pulmonary disease, cardiac hypertrophy and fibrosis, arthritis and neuronal injuries. Common to all these diseases is the involvement of fibrotic and inflammatory processes, i.e. processes greatly dependent on tissue remodelling, cell motility and epithelial-mesenchymal transition. Therefore, the basic biological mechanisms behind S100A4's effects are emerging. S100A4 belongs to the S100 family of proteins that contain two Ca2+-binding sites including a canonical EF-hand motif. S100A4 is involved in the regulation of a wide range of biological effects including cell motility, survival, differentiation and contractility. S100A4 has both intracellular and extracellular effects. Hence, S100A4 interacts with cytoskeletal proteins and enhances metastasis of several types of cancer cells. In addition, S100A4 is secreted by unknown mechanisms, thus, paracrinely stimulating a variety of cellular responses, including angiogenesis and neuronal growth. Although many cellular effects of S100A4 are well described, the molecular mechanisms whereby S100A4 elicits these responses remain largely unknown. However, it is likely that the intracellular and the extracellular effects involve distinct mechanisms. In this review, we explore the possible roles of S100A4 in non-cancer diseases and employ this knowledge to describe underlying biological mechanisms including a change in cellular phenotype towards less tightly adherent cells and activation of fibrotic processes that may explain this protein's involvement in multiple pathologies.
 ...
PMID:S100A4: a common mediator of epithelial-mesenchymal transition, fibrosis and regeneration in diseases? 1832 70

Preferentially expressed antigen of melanoma (PRAME) is expressed in a wide variety of tumors, but in contrast with most other tumor associated antigens, it is also expressed in leukemias. In a previous study, we showed that overexpression of PRAME induced apoptosis, inhibited cell proliferation and reduced tumorigenicity of leukemic cells in vivo. We also demonstrated that PRAME overexpression induced the repression of three genes (Hsp27, S100A4 and p21) associated with an unfavorable prognosis in leukemia. Here, we further investigated the mechanisms of PRAME-induced tumor suppression in vitro and in vivo. We performed a gene profiling study by analysing PRAME shRNA-silenced leukemic cells on high-density micro-arrays (Affymetrix) and found that PRAME altered the expression of two additional genes potentially involved in cancerogenesis and cancer progression: IL-8 and IGFBP-2. In a series of 28 acute myeloid leukemia pediatric patients, we observed that PRAME expression was associated with an increased leukemia-free survival. Importantly, the correlation between PRAME expression in leukemic cell lines and the decreased expression of Hsp27, S100A4, p21, IL-8 and the increased expression of IGFBP-2 was also observed in vivo, in leukemic patients. Our results suggest that the favorable prognosis of PRAME could be mediated, at least in part, by the modified expression of those genes.
 ...
PMID:Tumor associated antigen PRAME is a marker of favorable prognosis in childhood acute myeloid leukemia patients and modifies the expression of S100A4, Hsp 27, p21, IL-8 and IGFBP-2 in vitro and in vivo. 1845 7

AP-2alpha, interleukin-4 (IL-4), E-cadherin, fibulin 1D, p16(INK4alpha), PTEN, RKIP, and S100A4 are determinants (suppressors, except for S100A4) of cancer cell invasiveness and other traits of cancer progression, which are located upstream of matrix metalloproteinases (MMPs) in cell signaling pathways. We will refer to them as upstream cancer-progression determinants (UCPDs, for brevity). MMP-1, MMP-2, MMP-9, MMP-11, MMP-13, MMP-14, MMP-16, and MMP-19 are enhancers of cancer cell invasiveness and other traits of cancer progression, in MDA-MB-231 breast cancer cells. We are interested in pathway links from UCPDs to gene expression of cancer cell MMPs in MDA-MB-231 cells. To test models about these links, wild-type copies of UCPDs were transiently overexpressed and then MMP mRNAs were measured by reverse transcription real-time PCR. The present results show that each of eight UCPDs is linked to the gene expression of a unique set of MMPs. This indicates that the effects are sequence-specific and that each UCPD reaches these MMP expressions through different sets of signaling pathways. We have detected 20 new pathway links, 11 are downregulatory and nine are upregulatory; 15 are new links in any cell, and five are new links in breast cancer. In seven links, three cancer-progression suppressing UCPDs unexpectedly enhance the gene expression of five cancer-progression promoting MMPs.
 ...
PMID:New pathway links from cancer-progression determinants to gene expression of matrix metalloproteinases in breast cancer cells. 1865 63

The role of S100A4 in tumor progression and metastasis is well documented in numerous research articles and summarized in several reviews. Currently S100A4 is categorized as an essential metastasis-promoting factor whose production and secretion from "activated" stromal cells (fibroblasts, immunocytes and vascular cells) is initiated and stimulated by signals derived in tumor cells (cytokines, growth factors and others). However recent data gained from experimental and clinical studies significantly extend our knowledge on S100A4. Implications of S100A4 in various non-malignant pathological conditions have been demonstrated by number of research groups. In the mini-review we attempted to highlight the role of S100A4 in other than cancer important human pathologies, such as autoimmune inflammation (RA) and disorders in cardio-vascular, nervous and pulmonary systems. We suggest that diverse human diseases might have common molecular components and pathway(s). Possibly, inflammatory machinery and S100A4 as its intrinsic constituent could contribute to the pathogenesis of various disorders. Therefore, we presume that facts on S100A4 performance could be attractive for broad range of researchers and clinicians.
 ...
PMID:Metastasis-inducing S100A4 protein: implication in non-malignant human pathologies. 1878 56

Comparative microarray analyses provided insight into understanding transcript changes during cancer progression; however, a reproducible signature underlying breast carcinogenesis has yet to be little available. We utilized gene expression profiling to define molecular signatures associated with transformation and cancer progression in a series of isogenic human breast cancer cell lines including a normal, benign, noninvasive and invasive carcinoma. Clustering analysis revealed four distinct expression patterns based on upregulation or downregulation patterns. These profiles proved quite useful for describing breast cancer tumorigenesis and invasiveness. Downregulation of TNFSF7, S100A4, S100A7, S100A8, and S100A9 (calcium-binding protein family), and upregulation of kallikrein-5 and thrombospondin-1 were associated with transformation and progression of breast cancer cells. Importantly, downregulation of the genes was reversed by treatment with silencing inhibitors, implying the potential roles of epigenetic inactivation in breast carcinogenesis. Exogenous expressions of S100A8 and S100A9 inhibit growth in benign and noninvasive carcinoma cells, suggesting their negative role in cell proliferation. The data presented here may facilitate the identification and functional analyses of prognostic biomarkers for breast cancer.
 ...
PMID:Molecular signatures associated with transformation and progression to breast cancer in the isogenic MCF10 model. 1880 27

The function of S100A4, a member of the calcium-binding S100 protein family, has been associated with tumor invasion and metastasis. Although an essential pro-metastatic role of extracellular S100A4 in tumor progression has been demonstrated, the identification of the precise underlying mechanisms and protein partners (receptors) has remained elusive. To identify putative targets for extracellular S100A4, we screened a phage display peptide library using S100A4 as bait. We identified three independent peptide motifs with varying affinities for the S100A4 protein. Sequence analyses indicated that the most abundant peptide mimicked the F/YCC motif present in the epidermal growth factor domain of ErbB receptor ligands. S100A4 selectively interacted with a number of epidermal growth factor receptor (EGFR) ligands, demonstrating highest affinity for amphiregulin. Importantly, we found that S100A4 stimulated EGFR/ErbB2 receptor signaling and enhanced the amphiregulin-mediated proliferation of mouse embryonic fibroblasts. S100A4-neutralizing antibodies, as well as EGFR- and ErbB2 receptor-specific tyrosine kinase inhibitors, blocked these effects. The present results suggest that extracellular S100A4 regulates tumor progression by interacting with EGFR ligands, thereby enhancing EGFR/ErbB2 receptor signaling and cell proliferation. Structured digital abstract: * MINT-7256556: EGF (uniprotkb:P01133) binds (MI:0407) to S100A4 (uniprotkb:P26447) by far western blotting (MI:0047) * MINT-7256512: BC (uniprotkb:P35070) binds (MI:0407) to S100A4 (uniprotkb:P26447) by far western blotting (MI:0047) * MINT-7256485, MINT-7256618, MINT-7256636: AR (uniprotkb:P15514) binds (MI:0407) to S100A4 (uniprotkb:P26447) by far western blotting (MI:0047) * MINT-7256494: HB-EGF (uniprotkb:Q99075) binds (MI:0407) to S100A4 (uniprotkb:P26447) by far western blotting (MI:0047) * MINT-7256502: P53 (uniprotkb:P04637) binds (MI:0407) to S100A4 (uniprotkb:P26447) by far western blotting (MI:0047) * MINT-7256654: S100A2 (uniprotkb:P29034) binds (MI:0407) to AR (uniprotkb:P15514) by far western blotting (MI:0047) * MINT-7256693: S100A5 (uniprotkb:P33763) binds (MI:0407) to AR (uniprotkb:P15514) by far western blotting (MI:0047) * MINT-7256593: S100A4 (uniprotkb:P26447) binds (MI:0407) to BC (uniprotkb:P35070) by pull down (MI:0096) * MINT-7256567: S100A4 (uniprotkb:P26447) binds (MI:0407) to AR (uniprotkb:P15514) by pull down (MI:0096).
 ...
PMID:Epidermal growth factor receptor ligands as new extracellular targets for the metastasis-promoting S100A4 protein. 1974 Jan 7

The calcium-binding protein S100A4 promotes metastasis in several experimental animal models, and S100A4 protein expression is associated with patient outcome in a number of tumor types. S100A4 is localized in the nucleus, cytoplasm, and extracellular space and possesses a wide range of biological functions, such as regulation of angiogenesis, cell survival, motility, and invasion. In this review, we summarize the evidence connecting S100A4 and cancer metastasis and discuss the mechanisms by which S100A4 promotes tumor progression.
 ...
PMID:S100A4 and metastasis: a small actor playing many roles. 2001 88

Metastasis is a complex cascade of events involving a finely tuned interplay between malignant cells and multiple host factors. The transition from benign tumor growth to malignancy is manifested by the ability of tumor cells to traverse tissue barriers and invade surrounding tissues. Among a multitude of factors playing a role, the small calcium-binding protein S100A4 has been found to add to the invasive and metastatic capacity of cancer cells. However, the exact molecular function or mechanism by which S100A4 exerts its putative metastasis-promoting effects has not been fully elucidated, and the protein is most likely involved in several aspects of tumor progression. Several studies have recently described a direct interaction and/or reciprocal influence between S100A4 and the tumor suppressor protein p53. This corresponds to reports linking p53 to other S100-family members, especially S100B. The consequences are intriguing, connecting the metastasis-promoting protein S100A4 to the large set of important p53-mediated functions, with broad potential importance in cancer development and metastasis. In this review we emphasize the studies involving p53 and S100A4, elucidating and comparing reported results and conclusions.
 ...
PMID:Evaluation of potential interactions between the metastasis-associated protein S100A4 and the tumor suppressor protein p53. 2017 48

The S100 gene family encode low molecular weight proteins implicated in cancer progression. In this study, we analyzed the expression of four S100 genes in one cohort of patients with breast cancer and 16 S100 genes in a second cohort. In both cohorts, the expression of S100A8 and S1009 mRNA level was elevated in high-grade compared to low-grade tumors and in estrogen receptor-negative compared to estrogen receptor-positive tumors. None of the S100 transcripts investigated were significantly associated with the presence of lymph node metastasis. Notably, multiple S100 genes, including S100A1, S100A2, S100A4, S100A6, S100A8, S100A9, S100A10, S100A11, and S100A14 were upregulated in basal-type breast cancers compared to non-basal types. Using Spearman's correlation analysis, several S100 transcripts correlated significantly with each other, the strongest correlation has been found between S100A8 and S100A9 (r = 0.889, P < 0.001, n = 295). Of the 16 S100 transcripts investigated, only S100A11 and S100A14 were significantly associated with patient outcome. Indeed, these two transcripts predicted outcome in the cohort of patients that did not receive systemic adjuvant therapy. Based on our findings, we conclude that the different S100 genes play varying roles in breast cancer progression. Specific S100 genes are potential targets for the treatment of basal-type breast cancers.
 ...
PMID:The role of S100 genes in breast cancer progression. 2115 24


<< Previous 1 2 3 4 5 6 7 8 Next >>