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

Thioredoxin (Trx) and Trx reductase (TrxR) are redox-active proteins that participate in multiple cellular events, including growth promotion, apoptosis, and cytoprotection. Studies on overexpression of Trx and TrxR in human cancers have indicated a role of these proteins in tumor development. In this study, we analyzed the expression of TrxR in peripheral blood cells, tumor-transformed leukemia, and melanoma cells and found, in addition to abundant plasma membrane localization, that TrxR was released from these cells. Secretory cells were observed at the single cell level using a sensitive enzyme-linked immunospot assay. The release was inducible, and physiological stimulation of human monocytes by IFN-gamma, lipopolysaccharide, and interleukin 1alpha significantly increased the number of TrxR-secreting cells (P = 0.004). Secretion of TrxR followed the classical Golgi pathway, and it was confirmed by metabolic labeling using [35S]methionine and [35S]cysteine. TrxR was also detected for the first time in fresh healthy blood donor plasma (n = 21; median concentration, 18.0 ng/ml), with biological activity as determined by insulin reduction assay. These results highlight the role of extracellular Trx and TrxR during inflammation and tumor progression. Released Trx, with its active site motif containing amino acids Cys-X-X-Cys, was recently shown to have chemoattractant properties beside its previously described antioxidant and cocytokine activities. Regeneration of oxidized Trx requires available TrxR outside the cell, the presence and induction of which is described in this paper for normal and transformed cells.
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PMID:Thioredoxin reductase, a redox-active selenoprotein, is secreted by normal and neoplastic cells: presence in human plasma. 1078 96

Thioredoxin-1 is a redox protein that, when overexpressed, causes increased cancer-cell growth and inhibited apoptosis. Thioredoxin-1 expression has been reported to be increased in several human primary tumors, but its relationship to tumor progression and patient survival has not been established. We studied the expression of thioredoxin-1 as measured with immunohistochemical staining in paraffin-embedded human normal colonic mucosa, adenomatous polyps, and primary and metastatic colorectal cancer. Thioredoxin-1 expression was not increased in 12 colorectal adenomatous polyps, compared with 8 samples of normal colonic mucosa, but was significantly increased in 12 primary colorectal cancers (P <.01). Thioredoxin-1 expression was not significantly different in primary lymph-node metastases and the primary colorectal cancer. Using colorectal cancer samples from 37 subjects for whom survival data was available, we found that thioredoxin-1 expression increased with Dukes stage, although the association was not statistically significant (P =.077). We noted a significant association between thioredoxin-1 expression and patient survival (P =.004); higher score was associated with decreased survival. When adjusted for Dukes stage, thioredoxin-1 expression showed a statistically significant association with survival (P =.012). The work shows that increased thioredoxin-1 expression is a relatively late event in colorectal carcinogenesis and provides evidence in a small group of subjects with colorectal cancer of Dukes stages A through D that thioredoxin-1 expression may be an independent marker of patient prognosis.
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PMID:Increased expression of thioredoxin-1 in human colorectal cancer is associated with decreased patient survival. 1287 80

Thioredoxin (Trx) is a cellular redox enzyme that plays multiple roles in regulating cell growth and apoptosis. Jun activation domain-binding protein 1 (Jab1) was originally identified as a coactivator of activator protein 1 (AP-1) transcription and was also shown to promote degradation of the cyclin-dependent kinase inhibitor, p27Kip1. Recently, Jab1 expression was associated with the progression and poor prognosis of pituitary, epithelial ovarian, and breast cancers, suggesting that it plays a role in oncogenesis. Here, we report that Trx specifically interacts with and modulates the function of Jab1. Fluorescence resonance energy transfer and co-immunoprecipitation studies revealed that Trx and Jab1 colocalize and directly interact with each other. Further, Trx negatively regulates two important Jab1-controlled signaling pathways, activation of AP-1 transcription and degradation of p27Kip1, probably through a direct interaction between Trx and C-terminal of Jab1. The negative effect of Trx on AP-1 activity is Jab1-dependent, as it disappears when Jab1 levels are suppressed by an antisense approach. In addition, Trx competes with p27Kip1 for Jab1 binding. Taken together, our results suggest that Trx may regulate cell cycle and growth through a novel modulation of Jab1-mediated proliferation signals, further indicating that Trx may have the ability to control tumor progression.
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PMID:Thioredoxin modulates activator protein 1 (AP-1) activity and p27Kip1 degradation through direct interaction with Jab1. 1548 Apr 26

Thioredoxin (Trx) is a multifunctional redox protein that has growth-promoting and anti-apoptotic effects on cells and protects cells from endogenous and exogenous free radicals. Recently, altered expression of Trx has been reported in various cancers. In the present study, we investigated altered expression of Trx at the precancerous and carcinogenic phases during cholangiocarcinogenesis in a hamster cholangiocarcinoma (ChC) model, using semiquantitative immunohistochemical and Western blot analyses. Moreover, to determine if the results correlated well with those in human ChCs, we carried out a comparative immunohistochemical study for Trx in tissue-arrayed human ChCs with different grades of tumor cell differentiation. Trx was found highly expressed in the cytoplasm of dysplastic bile ducts with highly abnormal growth patterns and ChCs irrespective of tumor type or tumor cell differentiation. Overexpression of Trx at the precancerous and carcinogenic phases was further supported by significant elevation of Trx protein in Western blotting. The results from the hamster ChCs were in good agreement with those from human ChCs. Our results strongly suggested that the redox regulatory function of Trx plays an important role in bile duct cell transformation and tumor progression during cholangiocarcinogenesis.
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PMID:Expression of thioredoxin during progression of hamster and human cholangiocarcinoma. 1979 7

A human prostate cancer (PC3) xenograft model was established which reflects acquired in vivo resistance towards metronomic cyclophosphamide (CPA) treatment. Cell cultures of two in vivo resistant PC3 tumors were established which maintain chemoresistant phenotypes upon xenografting into mice. A comparative proteome analysis of the two resistant cell lines PC3-D3 and -D4 versus the non-resistant parental PC3 cell line by 2D-DIGE approach followed by MALDI-TOF-TOF analysis revealed a total of 25 differently expressed proteins. Validation of protein candidates by Western blot analysis of the corresponding in vivo tumor xenografts identified three differentially expressed proteins (thioredoxin containing protein 5, cathepsin B, and annexin A3). Thioredoxin containing protein 5 was up-regulated in resistant xenografts only upon in vivo CPA therapy. A truncated version of cathepsin B translocated into mitochondria in the resistant clones whereas it stays cytoplasmic in corresponding parental PC3 cells. Annexin A3 (ANXA3) presents a very interesting candidate which was found to be up-regulated both in vitro and in xenografts, with protein levels further increased by metronomic CPA treatment in vivo. It is noteworthy that independent studies in other epithelial cancers recently identified ANXA3 as cancer progression and resistance marker.
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PMID:In vivo chemoresistance of prostate cancer in metronomic cyclophosphamide therapy. 2021 15

Thyroid cancer is the second most common malignancy following breast cancer in Arab females. Thioredoxin (TRX) is a small multi-functional redox protein with both intracellular and extracellular functions. The protein exists in either a reduced form (thioredoxin-SH2) or an oxidized form (thioredoxin-S2). TRX acts as an enhancement for growth factors and stimulates the growth of cancer cells. In this study of thyroid neoplasms, involving 121 female and 62 male patients, expression of TRX and TRX-R was studied using purified mouse anti-human TRX monoclonal antibody and anti-human TRX-R antiserum from rabbits, respectively. In order to delineate tumour cell growth, proliferating cell nuclear antigen (PCNA) polyclonal antibody was used. Compared to normal thyroid tissue, expression of TRX and TRX-R was increased in the cytoplasm and nuclei of thyroid cancer cells. Furthermore, TRX expression correlated with that of TRX-R. Of the 183 thyroid neoplasms investigated, overexpression of TRX-R was found in different types of neoplasms. The majority of carcinomas showed a correlation between strongly positive TRX and TRX-R expression and neoplastic cellular proliferation, as measured by PCNA. This indicates that increased TRX and TRX-R expression may be associated with tumourigenesis by acting as an autocrine growth stimulus. This study suggests that TRX immunoreactivity in thyroid tumours is a function of malignancy and cancer progression. In addition, secreted TRX can also act as an extracellular growth factor for both normal and tumour cells and enhance the sensitivity of the cells. Furthermore, this study emphasizes the potential benefits of anti-TRX/TRX-R agents in cancer therapeutics in the treatment of thyroid cancer.
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PMID:Thioredoxin and thioredoxin reductase expression in thyroid cancer depends on tumour aggressiveness. 2039 95

Thioredoxin is a small redox-regulating protein, which plays crucial roles in maintaining cellular redox homeostasis and cell survival and is highly expressed in many cancers. The tumor environment is usually under either oxidative or hypoxic stress and both stresses are known up-regulators of thioredoxin expression. These environments exist in tumors because their abnormal vascular networks result in an unstable oxygen delivery. Therefore, the oxygenation patterns in human tumors are complex, leading to hypoxia/re-oxygenation cycling. During carcinogenesis, tumor cells often become more resistant to hypoxia or oxidative stress-induced cell death and most studies on tumor oxygenation have focused on these two tumor environments. However, recent investigations suggest that the hypoxic cycling occurring within tumors plays a larger role in the contribution to tumor cell survival than either oxidative stress or hypoxia alone. Thioredoxin is known to have important roles in both these cellular responses and several studies implicate thioredoxin as a contributor to cancer progression. However, only a few studies exist that investigate the regulation of thioredoxin in the hypoxic and cycling hypoxic response in cancers. This review focuses on the role of thioredoxin in the various states of tumor oxygenation.
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PMID:Thioredoxin and Cancer: A Role for Thioredoxin in all States of Tumor Oxygenation. 2428 Oct 68

In eukaryotes, overproduction of reactive oxygen species (ROS) causes oxidative stress, which contributes to chronic inflammation and cancer. MicroRNAs (miRNAs) are small, endogenously produced RNAs that play a major role in cancer progression. We established that overexpression of miR526b/miR655 promotes aggressive breast cancer phenotypes. Here, we investigated the roles of miR526b/miR655 in oxidative stress in breast cancer using in vitro and in silico assays. miRNA-overexpression in MCF7 cells directly enhances ROS and superoxide (SO) production, detected with fluorescence assays. We found that cell-free conditioned media contain extracellular miR526b/miR655 and treatment with these miRNA-conditioned media causes overproduction of ROS/SO in MCF7 and primary cells (HUVECs). Thioredoxin Reductase 1 (TXNRD1) is an oxidoreductase that maintains ROS/SO concentration. Overexpression of TXNRD1 is associated with breast cancer progression. We observed that miR526b/miR655 overexpression upregulates TXNRD1 expression in MCF7 cells, and treatment with miRNA-conditioned media upregulates TXNRD1 in both MCF7 and HUVECs. Bioinformatic analysis identifies two negative regulators of TXNRD1, TCF21 and PBRM1, as direct targets of miR526b/miR655. We validated that TCF21 and PBRM1 were significantly downregulated with miRNA upregulation, establishing a link between miR526b/miR655 and TXNRD1. Finally, treatments with oxidative stress inducers such as H2O2 or miRNA-conditioned media showed an upregulation of miR526b/miR655 expression in MCF7 cells, indicating that oxidative stress also induces miRNA overexpression. This study establishes the dynamic functions of miR526b/miR655 in oxidative stress induction in breast cancer.
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PMID:miR526b and miR655 Induce Oxidative Stress in Breast Cancer. 3143 Aug 59

Recently, several miRNAs have been revealed to play critical roles in oncogenesis and tumor progression of many cancers. Thioredoxin-1 (Trx-1) binding protein-2 (TBP-2) is an internal inhibitor of Trx-1, which plays the role in regulating oxidative stress, inhibiting cell growth, and promoting apoptosis. The expression of TBP-2 is usually decreased in cancer tissues. However, whether the miRNAs regulate the TBP-2 expression in lung cancer is still unclear. In this study, we examined the levels of TBP-2, miR-93, miR-373, and miR-17-5p in lung cancer tissues and their adjacent normal lung tissues of 36 patients. We found that the expressions of miR-93, miR-373, and miR-17-5p were higher, whereas the expression of TBP-2 mRNA and protein was significantly lower in lung cancer tissues compared with adjacent normal lung tissues. After the three miRNA mimics were transfected in the lung cancer cells, NCI-H460, the level of TBP-2 mRNA and TBP-2 protein was decreased. Then, the anti-cancer drug 5-fluorouracil was used to stimulate the NCI-H460 cells; the mRNA levels of miR-93, miR-373, and miR-17-5p were decreased, and the level of TBP-2 mRNA and protein was increased. Collectively, the above results suggest that miR-93, miR-373, and miR-17-5p negatively regulate the TBP-2 expression in lung cancer. This study may provide therapeutic targets with lung cancer.
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PMID:miR-93, miR-373, and miR-17-5p Negatively Regulate the Expression of TBP2 in Lung Cancer. 3242 73