Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.6.3.14 (ATP synthase)
 7,042 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Bcl-x(L) protein plays a role in breast cancer dormancy, promoting survival of cells in metastatic foci by counteracting the proapoptotic signals in the microenvironment. The aim of this study was to identify phenotypes mediated by Bcl-x(L) in breast cancer cells that enhance in vivo survival of clinical metastases. 435/Bcl-x(L) or 435/Neo human breast cancer cells were injected into the inguinal mammary gland of nude mice, and tumors, metastases in lymph node, lung, and bone, and bloodstream surviving cells were examined. Proteomic analysis identified 17 proteins that were overexpressed (more than twofold) or underexpressed (less than twofold) in metastases. A protein interaction program allowed us to functionally associate peroxiredoxin 3, peroxiredoxin 2, carbonyl reductase 3, and enolase 1, suggesting a role for cellular responses to oxidative stress in metastasis organ selection. The prediction included proteins involved in redox systems, kinase pathways, and the ATP synthase complex. Furthermore, the interaction of redox proteins with enolase 1 suggests a connection between glycolysis and antioxidant pathways, enabling achievement of a high metastatic activity. In conclusion, Bcl-x(L) mediates a phenotype in which redox pathways and glycolysis are coupled to protect breast cancer metastatic cells during transit from the primary tumor to the metastatic state.
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PMID:Bcl-x(L)-mediated changes in metabolic pathways of breast cancer cells: from survival in the blood stream to organ-specific metastasis. 1619 47

Liver metastasis is a major cause of poor survival of colorectal cancer patients. In order to identify the proteins associated with liver metastasis in colorectal cancer, we carried out two-dimensional gel electrophoresis-based comparative proteomic analysis of normal colon mucosa, primary colon cancer tissue and corresponding metastatic tumor tissue in liver. The proteins identified were further validated by immunohistochemical analysis of 67 quadruplet samples of normal colon primary colorectal cancer and normal liver-synchronous liver metastasis, and 251 colorectal cancers as well as in vitro invasion assay of the human colon cancer cell line, SNU-81. From proteomic assessment, the mitochondrial FoF1-ATP synthase (ATP synthase) alpha-subunit was identified as a protein that is upregulated in liver metastasis compared with the primary tumor. Immunohistochemical analyses confirmed a significant increase in the expression of ATP synthase alpha- and d-subunits in synchronous liver metastasis compared with primary tumor and normal mucosa, respectively. ATP synthase alpha- and d-subunits were overexpressed in 197 (78.5%) and 190 (75.7%), respectively, of the 251 colorectal cancers. The alpha- and d-subunits were significantly associated with liver metastasis (P < 0.05) as well as low histological grade (P < 0.0001). The d-subunit also correlated with venous invasion (P = 0.026) and distant metastasis (P = 0.032). In stage III cancers, d-subunit expression was independently associated with poor survival (P = 0.017). Furthermore, transfection of small interfering RNA targeted to ATP synthase alpha- and d-subunits resulted in decreased in vitro invasiveness of the human colon cancer cell line. Our overall findings demonstrate that increased ATP synthase is associated with liver metastasis of colorectal cancer.
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PMID:Identification of mitochondrial FoF1-ATP synthase involved in liver metastasis of colorectal cancer. 1755 25

Metastasis is a complex, multistep process by which a cancer cell leaves the primary tumor, travels to a distant site via the circulatory system, and establishes a secondary cancer. A deeper understanding of the molecular events underlying metastasis will provide information that will be useful for the development of new diagnostic and therapeutic strategies. The B16 and B16F10 mouse melanoma cell lines are widely used as model system for studying many aspects of cancer biology including metastasis. Compared with B16, which has a low metastatic potential, the highly metastatic cell line B16F10 displayed a higher metastatic ability along with higher expression levels of the metastasis-associated phosphatase of regenerating liver-3 (PRL-3). B16 cells transfected with PRL-3 cDNA (B16-PRL3) had metastatic abilities comparable to those of Bl16F10 cells. To study the molecular mechanisms that underlie metastasis, the proteomes of the B16, B16F10, and B16-PRL3 cell lines were compared using two-dimensional differential in-gel electrophoresis. Proteins that varied significantly in levels between these cell lines were selected and identified using mass spectrometry. Interestingly, many proteins, especially those present in membrane fractions, were similarly up- or downregulated in both the Bl16F10 and B16-PRL3 cells lines compared to B16 cell lines. The list of similarly regulated proteins included heat shock protein 70, fascin-1, septin-6, ATP synthase beta subunit, and bone morphogenic protein receptor type IB. These proteins may play a causal role in PRL-3-mediated metastasis. These investigations open an avenue for the further characterization of the molecular mechanisms that underlie metastasis.
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PMID:Comparative proteomic analysis of mouse melanoma cell line B16, a metastatic descendant B16F10, and B16 overexpressing the metastasis-associated tyrosine phosphatase PRL-3. 1980 91

A sentinel lymph node (SLN) is the first lymph node that receives drainage from a primary tumor. According to their physiological and biomechanical characteristics, we hypothesized that SLN contains lymphatic endothelial cells (LEC) that are constantly loaded with high levels of shear stress, which might contribute to the production of a suitable environment for micrometastasis within them. To test this hypothesis, we investigated the effects of shear stress stimulation on the expression of adhesion molecules on human LEC isolated from the lymph vessels nearest the SLN of breast cancers, and on the release of ATP from human LEC. The study clarified that the shear stress stimulation produced a significant increase of ICAM-1 expression at protein and mRNA levels in human LEC. Next, we examined whether the shear stress-mediated increase of ICAM-1 expression accelerates the attachment of carcinoma cells to human LEC. Finally, in in vivo experiments, we evaluated whether exogenous ATP facilitates the expression of carcinoma cell-ligated adhesion molecules in rat SLN. In conclusion, shear stress stimulation induces ICAM-1 expression on human LEC by activating cell surface F(1) /F(O) ATP synthase, which might contribute to the development of a premetastatic environment within SLN.
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PMID:Pivotal roles of shear stress in the microenvironmental changes that occur within sentinel lymph nodes. 2246 28