Abstract：
:Pancreatic ductal adenocarcinoma (PDAC) remains one of the most lethal cancers largely due to disseminated disease at the time of presentation. Here, we investigated the role and mechanism of action of the metastasis-associated protein anterior gradient 2 (AGR2) in the pathogenesis of pancreatic cancer. AGR2 was induced in all sporadic and familial pancreatic intraepithelial precursor lesions (PanIN), PDACs, circulating tumor cells, and metastases studied. Confocal microscopy and flow cytometric analyses indicated that AGR2 localized to the endoplasmic reticulum (ER) and the external surface of tumor cells. Furthermore, induction of AGR2 in tumor cells regulated the expression of several ER chaperones (PDI, CALU, RCN1), proteins of the ubiquitin-proteasome degradation pathway (HIP2, PSMB2, PSMA3, PSMC3, and PSMB4), and lysosomal proteases [cathepsin B (CTSB) and cathepsin D (CTSD)], in addition to promoting the secretion of the precursor form pro-CTSD. Importantly, the invasiveness of pancreatic cancer cells was proportional to the level of AGR2 expression. Functional downstream targets of the proinvasive activity of AGR2 included CTSB and CTSD in vitro, and AGR2, CTSB, and CTSD were essential for the dissemination of pancreatic cancer cells in vivo. Taken together, the results suggest that AGR2 promotes dissemination of pancreatic cancer and that its cell surface targeting may permit new strategies for early detection as well as therapeutic management.
journal_name
Cancer Resjournal_title
Cancer researchauthors
Dumartin L,Whiteman HJ,Weeks ME,Hariharan D,Dmitrovic B,Iacobuzio-Donahue CA,Brentnall TA,Bronner MP,Feakins RM,Timms JF,Brennan C,Lemoine NR,Crnogorac-Jurcevic Tdoi
10.1158/0008-5472.CAN-11-1367subject
Has Abstractpub_date
2011-11-15 00:00:00pages
7091-102issue
22eissn
0008-5472issn
1538-7445pii
0008-5472.CAN-11-1367journal_volume
71pub_type
杂志文章相关文献
CANCER RESEARCH文献大全abstract：:Allelic loss of chromosome region 3p21.3 occurs early and frequently in non-small-cell lung cancer, and numerous tumor suppressor genes at this locus may be targets of inactivation. Using an incident case series study of non-small-cell lung cancer, we sought to determine the prevalence of loss of heterozygosity (LOH) ...
journal_title：Cancer research
pub_type： 杂志文章
doi：10.1158/0008-5472.CAN-04-2558
更新日期：2004-12-01 00:00:00
abstract：:Testicular germ cell cancer is one of the very few cancers that are highly sensitive to and curable by cisplatin-based chemotherapy even in an advanced stage. However, in a few cases resistance to cisplatin occurs and patients subsequently die from progressive disease. The molecular basis for this resistance remains t...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：2003-01-15 00:00:00
abstract：:Although the cyclin-dependent kinases CDK4 and CDK6 play fundamental roles in cancer, the specific pathways and downstream targets by which they exert their tumorigenic effects remain elusive. In this study, we uncover distinct and novel functions for these kinases in regulating tumor formation and metastatic coloniza...
journal_title：Cancer research
pub_type： 杂志文章
doi：10.1158/0008-5472.CAN-20-2121
更新日期：2020-12-28 00:00:00
abstract：:Loss of function of the tumor suppressor protein p53 represents a very frequent event in human carcinogenesis, but the molecular mechanisms linking impaired p53 activity to increased cell malignancy are still incompletely understood. p53 is normally involved in both cell cycle control and the induction of cell death a...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：2000-08-15 00:00:00
abstract：:Approximately 25% of breast cancers do not express the estrogen receptor-α (ERα) and consequently do not respond to endocrine therapy. In these tumors, ERα repression is often due to epigenetic modifications such as methylation and histone deacetylation. For this reason, we investigated the ability of the histone deac...
journal_title：Cancer research
pub_type： 杂志文章
doi：10.1158/0008-5472.CAN-10-2458
更新日期：2011-03-01 00:00:00
abstract：:Non-small cell lung cancer (N-SCLC) is generally unresponsive to chemotherapy even without previous drug treatment, as opposed to small cell lung cancer (SCLC), which is initially responsive to chemotherapy. The mechanisms of this intrinsic resistance are unknown. This study was designed to investigate the role of DNA...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1995-11-01 00:00:00
abstract：:A transplantable bladder tumor (Chapman R-4909) of the rat, when first received in our laboratory, grew with a complex histopathology. The predominant component was transitional cell carcinoma, but there were foci of keratinization, including pearl formation, and foci of a less well-defined cystic appearance. We repor...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1976-08-01 00:00:00
abstract：:Expression of the c-Myc oncoprotein is affected by conserved threonine 58 (T58) and serine 62 (S62) phosphorylation sites that help to regulate c-Myc protein stability, and altered ratios of T58 and S62 phosphorylation have been observed in human cancer. Here, we report the development of 3 unique c-myc knock-in mice ...
journal_title：Cancer research
pub_type： 杂志文章
doi：10.1158/0008-5472.CAN-10-1032
更新日期：2011-02-01 00:00:00
abstract：:The breast cancer susceptibility gene BRCA2 is expressed in a wide range of tissues as an 11-kb mRNA transcript encoding a 3418-amino acid protein, which is involved in the response to DNA damage. To obtain a better molecular characterization of BRCA2 expression in breast tissue, we analyzed full-length BRCA2 mRNA by ...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1999-06-01 00:00:00
abstract：:A role for the immune system in controlling the progression of solid tumors has been established in several mouse models. However, the effect of immune responses and tumor escape on patient prognosis in the context of human cancer is poorly understood. Here, we investigate the cellular and molecular parameters that co...
journal_title：Cancer research
pub_type： 杂志文章
doi：10.1158/0008-5472.CAN-08-2654
更新日期：2009-03-15 00:00:00
abstract：:The majority of patients with colon cancer will develop advanced disease, with the liver being the most common site of metastatic disease. Patients with increased numbers of tumor-infiltrating lymphocytes in primary colon tumors and liver metastases have improved outcomes. However, the molecular factors that could emp...
journal_title：Cancer research
pub_type： 杂志文章
doi：10.1158/0008-5472.CAN-16-1655
更新日期：2017-04-15 00:00:00
abstract：:Approximately one third of breast cancers grow independently of estrogen, lack detectable estrogen receptor (ER) protein, and rarely respond to hormonal treatment. Previous studies correlated the lack of ER gene expression in ER-negative breast tumor cells with hypermethylation of a CpG island in the 5' region of the ...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1995-06-01 00:00:00
abstract：:Applications of mathematical modeling can improve outcome predictions of cancer therapy. Here we present a kinetic model incorporating effects of radiosensitivity, tumor repopulation, and dead-cell resolving on the analysis of tumor volume regression data of 80 cervical cancer patients (stages 1B2-IVA) who underwent r...
journal_title：Cancer research
pub_type： 杂志文章
doi：10.1158/0008-5472.CAN-09-2501
更新日期：2010-01-15 00:00:00
abstract：:We have investigated the behavior of dissociated cells of a moderately differentiated Longnecker transplantable pancreatic acinar carcinoma (Longnecker et al., Cancer Lett., 7: 197-202, 1979) maintained in vitro on acellular seminiferous tubular basement membranes of rat testis. The tumor cells, which grow as solid ma...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1986-01-01 00:00:00
abstract：:The breast- and ovarian-specific tumor suppressor BRCA1 has been implicated in numerous cellular processes, including transcription, ubiquitination, and DNA repair. Its tumor suppression activity is tightly linked to that of BARD1, a protein that heterodimerizes with BRCA1. It has been previously shown that BRCA1 bind...
journal_title：Cancer research
pub_type： 杂志文章
doi：10.1158/0008-5472.CAN-05-3296
更新日期：2006-02-15 00:00:00
abstract：:Constitutively photomorphogenic 1 (COP1), a RING finger ubiquitin ligase with substrates including c-Jun and p53, was recently found to be overexpressed in a number of breast and ovarian tumor samples. In addition to its E3 activity, COP1 was also shown to be able to inhibit activator protein 1 (AP-1) transcription. T...
journal_title：Cancer research
pub_type： 杂志文章
doi：10.1158/0008-5472.CAN-05-0423
更新日期：2005-07-01 00:00:00
abstract：:A metastatic renal cell carcinoma (RCC) tumor model xenograft that expresses the targetable, membrane-bound tumor-associated antigen carbonic anhydrase type 9 (CA IX) is described. The xenograft, established from a high-grade type-2 chromophil RCC (cRCC), has been serially transplanted in immune compromised mice, in w...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：2003-08-15 00:00:00
abstract：:RAF kinase inhibitor protein (RKIP) is a seminal regulator of intracellular signaling and exhibits both antimetastatic and antitumorigenic properties. Decreased expression of RKIP has been described in several human malignancies, including acute myelogenous leukemia (AML). As the mechanisms leading to RKIP loss in AML...
journal_title：Cancer research
pub_type： 杂志文章
doi：10.1158/0008-5472.CAN-15-3049
更新日期：2016-06-15 00:00:00
abstract：:p63, a recently identified member of the p53 gene family, encodes multiple products with transactivating, death-inducing, and dominant-negative activities. To explore the penetrance of p63 in bladder carcinogenesis, we performed expression and mutation analyses of two major isotypes, TAp63 and deltaNp63, in 63 bladder...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：2000-07-01 00:00:00
abstract：:Vinyl chloride (VC) induces angiosarcomas of the liver (ASL) and hepatocellular carcinomas (HCCs) in humans and rodents. We examined the presence of p53 gene mutations in ASL and HCC induced by VC in Sprague Dawley rats; 25 ASL and eight HCCs were analyzed for point mutations in exons 5-8, using PCR amplification, sin...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1997-05-01 00:00:00
abstract：:We have previously reported that rodent tumor cell lines secrete a potent vascular permeability factor with a molecular weight of 34,000-42,000 (Senger et al. Tumor cells secrete a vascular permeability factor that promotes accumulation of ascites fluid. Science (Wash. DC), 219: 983-985, 1983). This tumor-secreted vas...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1986-11-01 00:00:00
abstract：:Optimal delivery of chemotherapy intensity is dependent on host- and tumor-specific characteristics. In this article, the chemotherapy late intensity schedule is revised to account for tumor growth instability, where a small tumor cell fraction emerges that exhibits a higher proliferation rate than the parent strain. ...
journal_title：Cancer research
pub_type： 杂志文章
doi：10.1158/0008-5472.CAN-09-0653
更新日期：2009-11-01 00:00:00
abstract：:To test the hypothesis that genetic instability correlates with malignant potential, we compared the rate of generation of marker chromosomal abnormalities in clones of B16 F1 and B16 F10 murine melanoma. These rates were estimated through an adaptation of fluctuation analysis of Luria and Delbruck (S. E. Luria and M....
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1987-07-15 00:00:00
abstract：:The lethal effects of bleomycin and its derivative, peplomycin, were determined for HeLa S3 cells grown in multicell spheroids cocultured with human diploid fibroblasts. Both drugs were less effective for cells in spheroids than for cells grown exponentially in monolayers. However, HeLa cells from spheroids exposed to...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1984-04-01 00:00:00
abstract：:The expression of different components of the plasminogen activator (PA)/plasmin system was explored in a series of colorectal neoplasia. We have found that urokinase (uPA) and urokinase receptor (uPA-R) gene expression is upregulated in adenomas and carcinomas, and that uPA/uPA-R production is confined to stromal cel...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1995-10-15 00:00:00
abstract：:A mammalian cell expression plasmid, pH beta-Aro, containing the human placenta aromatase complementary DNA was constructed. The prepared plasmid was used to transfect breast cancer cells (MCF-7), noncancerous breast cells (HBL-100), and Chinese hamster ovary cells by a stable expression method. While the maximum velo...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1990-11-01 00:00:00
abstract：:Dehydroepiandrosterone, an adrenal steroid that has been reported to be produced in subnormal amounts and found in lower plasma concentrations in women with benign and malignant breast tumors, protects cultured rat liver epithelial-like cells against aflatoxin B1-induced cytotoxicity and protects hamster embryonic fib...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1975-09-01 00:00:00
abstract：:Epidemiologic studies linking high serum iron with cancer risks are limited and inconclusive, despite evidence implicating body iron in human carcinogenesis. A cohort of 309,443 adults in Taiwan who had no history of cancer had serum iron levels tested at the time of recruitment (1997-2008). Initially measured iron le...
journal_title：Cancer research
pub_type： 杂志文章
doi：10.1158/0008-5472.CAN-14-0360
更新日期：2014-11-15 00:00:00
abstract：:1-Nitropyrene, a direct-acting mutagenic component of extracts of diesel exhaust and ambient air particulates, is one of the major nitroarenes found in products of incomplete combustion. Injection of this compound into newborn Sprague-Dawley-derived CD rats at 100 mumol/kg body weight s.c. once a week for 8 weeks indu...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1984-03-01 00:00:00
abstract：:We have analyzed the mechanism of activation of two human ras oncogenes. We have also identified a rasN gene from a human gastric adenocarcinoma which efficiently induced both morphological transformation and tumorigenicity of NIH3T3 cells in a transfection assay. The rasN gene in tumor tissue DNA did not appear to be...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1986-09-01 00:00:00
