Abstract：
:Metastatic cases of breast cancer pose the primary challenge in clinical management of this disease, demanding the identification of effective therapeutic strategies that remain wanting. In this study, we report that elevated levels of α-tubulin acetylation are a sufficient cause of metastatic potential in breast cancer. In suspended cell culture conditions, metastatic breast cancer cells exhibited high α-tubulin acetylation levels that extended along microtentacle (McTN) protrusions. Mutation of the acetylation site on α-tubulin and enzymatic modulation of this posttranslational modification exerted a significant impact on McTN frequency and the reattachment of suspended tumor cells. Reducing α-tubulin acetylation significantly inhibited migration but did not affect proliferation. In an analysis of more than 140 matched primary and metastatic tumors from patients, we found that acetylation was maintained and in many cases increased in lymph node metastases compared with primary tumors. Proteomic analysis of an independent cohort of more than 390 patient specimens further documented the relationship between increased α-tubulin acetylation and the aggressive behaviors of basal-like breast cancers, with a trend toward increased risk of disease progression and death in patients with high-intensity α-tubulin acetylation in primary tumors. Taken together, our results identify a tight correlation between acetylated α-tubulin levels and aggressive metastatic behavior in breast cancer, with potential implications for the definition of a simple prognostic biomarker in patients with breast cancer.
journal_name
Cancer Resjournal_title
Cancer researchauthors
Boggs AE,Vitolo MI,Whipple RA,Charpentier MS,Goloubeva OG,Ioffe OB,Tuttle KC,Slovic J,Lu Y,Mills GB,Martin SSdoi
10.1158/0008-5472.CAN-13-3563subject
Has Abstractpub_date
2015-01-01 00:00:00pages
203-15issue
1eissn
0008-5472issn
1538-7445pii
0008-5472.CAN-13-3563journal_volume
75pub_type
杂志文章相关文献
CANCER RESEARCH文献大全abstract：:Nile blue derivatives have been shown to be potentially effective photosensitizers for photodynamic therapy of malignant tumors. Results of a previous study suggested that the high accumulation of these dyes in cells may be the result of dye aggregation, partition in membrane lipids, and/or sequestration in subcellula...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1991-05-15 00:00:00
abstract：:Soluble membrane fractions derived from polyoma tumor cells trigger lymphocytes, derived from polyoma-immunized animals, but not from nonimmunized controls, to release the lymphokine, macrophage migration-inhibitory factor. The reaction can be blocked by sera from polyoma-bearing animals. Absorption of these sera with...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1986-10-01 00:00:00
abstract：:Retinoic acid (RA) is a potent in vitro inhibitor of cell proliferation in various malignant cell lines. The exact mechanisms of its actions, however, are not fully understood. To further elucidate the nature of this inhibition, we investigated the effects of RA in an estrogen receptor-negative human breast cancer cel...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1996-04-01 00:00:00
abstract：:Methodology for identifying tumor-associated antigens recognized by T cells has been successfully used to clone antigens from melanoma cells. Similar efforts for nonmelanoma tumors have had limited success with few antigens identified. To identify potentially relevant tumor-associated antigens expressed in renal cell ...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：2001-07-15 00:00:00
abstract：:Fumitremorgin C (FTC) is a potent and specific chemosensitizing agent in cell lines selected for resistance to mitoxantrone that do not overexpress P-glycoprotein or multidrug resistance protein. The gene encoding a novel transporter, the breast cancer resistance protein (BCRP), was recently found to be overexpressed ...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：2000-01-01 00:00:00
abstract：:Drug resistance is a major problem in the successful treatment of cancer. Resistance to one drug is often associated with cross-resistance to other anticancer agents. This is commonly seen with the "natural product" anticancer drugs such as the Vinca alkaloids and anthracyclines. In experimental systems, specific chan...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1985-07-01 00:00:00
abstract：:Although the zinc finger transcription factor Krüppel-like factor 4 (KLF4) has been shown to be a negative regulator of cell proliferation, the mechanisms underlying the posttranslational modification of KLF4, especially at the level of protein degradation, are poorly understood. Here, we show that KLF4 protein levels...
journal_title：Cancer research
pub_type： 杂志文章
doi：10.1158/0008-5472.CAN-05-2059
更新日期：2005-11-15 00:00:00
abstract：:Thmidine (TdR) incorporation into DNA increased in the livers and spleens of rats bearing Yoshida sarcoma (solid type) or AH130 (solid type). TdR kinase and DNA polymerase activities increased in the serum, liver, and spleen of these rats, while thymidine monophosphate kinase activity increased appreciably only in the...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1975-03-01 00:00:00
abstract：:The development of prophylactic cancer vaccines that protect healthy hosts from tumor development leaves open the question whether such vaccines are also effective against established tumors and metastases. We tested the therapeutic activity of a proven prophylactic anti-HER-2/neu vaccine against successive stages of ...
journal_title：Cancer research
pub_type： 杂志文章
doi：10.1158/0008-5472.CAN-07-2499
更新日期：2007-11-15 00:00:00
abstract：:Expression and function of the Fas apoptotic pathway was investigated in normal and malignant human breast epithelial cells. Nontransformed mammary epithelial cell lines all expressed high levels of Fas mRNA and protein, but only one of seven breast cancer cell lines (T47D) expressed high levels of Fas. Apoptosis was ...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1996-10-15 00:00:00
abstract：:Multiple DNA microsatellites with frequent loss of heterozygosity (LOH) in melanomas have been demonstrated. The finding that free DNA is enriched in blood of melanoma patients prompted studies to determine whether tumor-specific DNA, such as DNA microsatellites exhibiting LOH, can be detected in blood and have clinic...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1999-04-01 00:00:00
abstract：:The relationship between nitric oxide synthase II (NOS II) inducibility and the metastatic ability of UV-2237 murine fibrosarcoma cells was determined. Highly metastatic cells survived to produce numerous lung metastases after i.v. injection in syngeneic C3H/HeN mice, whereas poorly metastatic cells did not. Highly me...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1999-05-01 00:00:00
abstract：:The WWOX (WW domain containing oxidoreductase) gene was recently identified as a candidate tumor suppressor gene at 16q23.3-24.1, a chromosome region that spans the common fragile site FRA16D. To evaluate the potential role of the WWOX gene in esophageal squamous cell carcinomas, we examined 36 tumors for genetic alte...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：2002-04-15 00:00:00
abstract：:The pharmacokinetics of melphalan following high-dose p.o. administration were determined in 17 patients with various malignancies for the purpose of assessing interpatient and intrapatient pharmacokinetic variability. All patients underwent bone marrow harvest on day -8 (relative to bone marrow reinfusion). On days -...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1989-03-01 00:00:00
abstract：:Tumor-specific rosette-forming cells reactive to solubilized tumor antigens conjugated to autologous erythrocytes were quantitated by flow cytofluorometry. Leukocytes from a high frequency of the patients (greater than 70%) with squamous cell carcinoma of the head and neck (SQCC) formed rosettes to the conjugated SQCC...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1982-07-01 00:00:00
abstract：:The effect of culture conditions on the glutamylation of methotrexate by intact H35 hepatoma cells and folylpolyglutamate synthetase (FPGS) activity in the corresponding crude extracts has been examined. The rate of cellular glutamylation of methotrexate observed in rapidly dividing cultures was 4-fold higher than con...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1988-05-01 00:00:00
abstract：:Malignant brain tumors present a major therapeutic challenge because no selective or efficient treatment is available. Here, we demonstrate that intratumoral administration of human alpha-lactalbumin made lethal to tumor cells (HAMLET) prolongs survival in a human glioblastoma (GBM) xenograft model, by selective induc...
journal_title：Cancer research
pub_type： 杂志文章
doi：10.1158/0008-5472.can-03-2661
更新日期：2004-03-15 00:00:00
abstract：:Increased neovascularization and vascular hyperpermeability are integral processes in tumors, and various therapeutic strategies seek to reverse the angiogenic phenotype. Long-circulating liposomes extravasate in tumors such as the rat 9L gliosarcoma and accumulate in perivascular areas. Under such conditions, liposom...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：2002-05-01 00:00:00
abstract：:Estradiol and progesterone receptors were assayed in tumors from 79 patients with primary colorectal and 56 patients with stomach adenocarcinomas. Eighteen of 79 colorectal cancers contained estradiol receptor, while 34 specimens were positive for progesterone receptor. In stomach cancer, the positive samples were 8 f...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1984-10-01 00:00:00
abstract：:A glomerulopathy in hamsters bearing human epithelial tumors is described. The tumors resulted from the s.c. implantation of human heteroploid cells (MA160) derived originally from a benign prostatic adenoma. The renal immunomorphological and ultrastructural changes include expansion of mesangial matrix and cellularit...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1979-02-01 00:00:00
abstract：:Rhabdomyosarcomas are the most frequent malignant soft tissue tumors of childhood; however, because current multimodality treatments fail to improve the poor survival rate of children with metastatic rhabdomyosarcoma, new treatments are required. We previously identified the gamma-subunit of the fetal acetylcholine re...
journal_title：Cancer research
pub_type： 杂志文章
doi：10.1158/0008-5472.CAN-05-0542
更新日期：2006-01-01 00:00:00
abstract：:The correlation between telomerase activity, telomere lengths, and cellular replicative capacity has led to the theory that maintenance of telomere lengths by telomerase acts as a molecular clock to control replicative capacity and senescence. Regulation of this molecular clock may have applications in the treatment o...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1998-09-15 00:00:00
abstract：:Non-small cell lung cancer patients carrying oncogenic EGFR mutations initially respond to EGFR-targeted therapy, but later elicit minimal response due to dose-limiting toxicities and acquired resistance. EGF816 is a novel, irreversible mutant-selective EGFR inhibitor that specifically targets EGFR-activating mutation...
journal_title：Cancer research
pub_type： 杂志文章
doi：10.1158/0008-5472.CAN-15-2581
更新日期：2016-03-15 00:00:00
abstract：:Retinoic acid inhibits the proliferation of the murine melanoma clone S91-C-2 cells, enhances the glycosylation of specific cell surface sialoglycoproteins, and stimulates sialytransferase activity. Mutant clones, selected from the S91-C-2 cells for resistance to the growth-inhibitory effect of retinoic acid, were use...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1984-12-01 00:00:00
abstract：:Lactoperoxidase-catalyzed metabolism of N-hydroxy-N-2-fluorenylacetamide (N-OH-2-FAA) may be via one-electron oxidation to nitroxyl free radical which dismutates to equimolar N-acetoxy-N-2-fluorenylacetamide and 2-nitrosofluorene (2-NOF) and/or a Br(-)-dependent oxidative cleavage to 2-NOF. Hence, the 2-NOF:N-acetoxy-...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1986-12-01 00:00:00
abstract：:Concanavalin A (Con A) binding of fixed malignant and nonmalignant C3H/He mouse mammary epithelia in monolayer cultures was examined with markers and labels of various sizes. In Con A-mediated hemadsorption, high epithelial cell densities resulted in the adsorbance of more guinea pig red blood cells per culture dish b...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1984-02-01 00:00:00
abstract：:Cancer is a major health concern and a leading cause of mortality. The reliable identification of carcinogens and understanding of carcinogenicity has become a main focus of biomedical research and regulatory toxicology. While biomedical research applies cellular in vitro methods to uncover the underlying mechanisms c...
journal_title：Cancer research
pub_type： 杂志文章
doi：10.1158/0008-5472.CAN-19-2822
更新日期：2020-04-15 00:00:00
abstract：:Acute promyelocytic leukemia is associated with a t(15;17) translocation that generates a fusion product between PML and the retinoic acid receptor alpha. Recently, PML was shown to concentrate within subnuclear domains, referred to as nuclear bodies, that are disorganized in acute promyelocytic leukemia cells. This o...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1995-04-01 00:00:00
abstract：:Infection of tumor cells by herpes simplex virus 1 (HSV-1) results in cell destruction and production of progeny virion in a process referred to as viral oncolysis. In this study, an HSV-1 mutant (HSV1yCD) was engineered such that the viral ribonucleotide reductase gene is disrupted by sequences encoding yeast cytosin...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：2001-07-15 00:00:00
abstract：:We have studied the effects of low-power-density microwave (MW) radiation (continuous and pulsed wave with average power density of 10 milliwatts/sq cm and range of 5 to 50 milliwatts/sq cm; frequency, 1.0 GHz) on the uptake and action of methotrexate (MTX), the inhibition of DNA synthesis in L1210 murine leukemia cel...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1980-04-01 00:00:00
