Abstract:
:Kras is a decisive oncogene in pancreatic ductal adenocarcinoma (PDAC). PIN1 is a key effector involved in the Kras/ERK axis, synergistically mediating various cellular events. However, the underlying mechanism by which PIN1 promotes the development of PDAC remains unclear. Here we sought to elucidate the effect of PIN1 on redox homeostasis in Kras-driven PDAC. PIN1 was prevalently upregulated in PDAC and predicted the prognosis of the disease, especially Kras-mutant PDAC. Downregulation of PIN1 inhibited PDAC cell growth and promoted apoptosis, partially due to mitochondrial dysfunction. Silencing of PIN1 damaged basal mitochondrial function by significantly increasing intracellular ROS. Furthermore, PIN1 maintained redox balance via synergistic activation of c-Myc and NRF2 to upregulate expression of antioxidant response element driven genes in PDAC cells. This study elucidates a new mechanism by which Kras/ERK/NRF2 promotes tumor growth and identifies PIN1 as a decisive target in therapeutic strategies aimed at disturbing the redox balance in pancreatic cancer. SIGNIFICANCE: This study suggests that antioxidation protects Kras-mutant pancreatic cancer cells from oxidative injury, which may contribute to development of a targeted therapeutic strategy for Kras-driven PDAC by impairing redox homeostasis.
journal_name
Cancer Resjournal_title
Cancer researchauthors
Liang C,Shi S,Liu M,Qin Y,Meng Q,Hua J,Ji S,Zhang Y,Yang J,Xu J,Ni Q,Li M,Yu Xdoi
10.1158/0008-5472.CAN-18-1968subject
Has Abstractpub_date
2019-01-01 00:00:00pages
133-145issue
1eissn
0008-5472issn
1538-7445pii
0008-5472.CAN-18-1968journal_volume
79pub_type
杂志文章相关文献
CANCER RESEARCH文献大全abstract::Most cancer-associated single-nucleotide polymorphisms (SNP) identified using genome-wide association studies are located outside of protein-coding regions, and their significance and mode of action have been a source of continuing debate. One proposed mechanism of action of the SNPs is that they would affect the acti...
journal_title:Cancer research
pub_type: 杂志文章,评审
doi:10.1158/0008-5472.CAN-13-0789
更新日期:2013-07-15 00:00:00
abstract::Insulin-like growth factor I action has been implicated in the pathogenesis of many different malignancies, including breast cancer. Insulin-like growth factor I receptors (IGF-IRs) are overexpressed in virtually all breast cancer cell lines, in which they are believed to enhance growth and inhibit apoptosis. In this ...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1998-03-15 00:00:00
abstract::Groups of 15 mice of three different laboratory strains (BALB/c, C3H/He, DBA/2) were fed on a low iron diet (5 mg iron/kg diet), and three similar groups of 15 mice were maintained on a normal iron diet (312 mg iron/kg diet). When the low iron diet group became iron deficient, tumor cells (5 x 10(5) cells/mouse) of CA...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1988-08-01 00:00:00
abstract::The failure and/or toxicity of conventional therapies for many types of human cancers underscore the need for development of safe and effective alternative treatments. Toward this goal, we describe the direct oncolytic activity of RNA-based vectors derived from poliovirus, termed replicons, which are genetically incap...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:2001-12-01 00:00:00
abstract::Mounting clinical and preclinical evidence supports a key role for sustained adrenergic signaling in the tumor microenvironment as a driver of tumor growth and progression. However, the mechanisms by which adrenergic neurotransmitters are delivered to the tumor microenvironment are not well understood. Here we present...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-16-1701
更新日期:2018-06-15 00:00:00
abstract::Although ethanol has generally not been found to induce cancer in experimental animals, the consumption of alcoholic beverages has been linked to increased risks of several cancers in humans. Risks of oral, pharyngeal, laryngeal, esophageal, and liver cancer are elevated among drinkers, typically in proportion to the ...
journal_title:Cancer research
pub_type: 杂志文章,评审
doi:
更新日期:1992-04-01 00:00:00
abstract::We previously reported that MX2, a new morpholino anthracycline, showed marked effects on pleiotropic drug-resistant sublines of murine P388 leukemia in vivo as well as in vitro. In this study we examine the in vitro cytotoxicity against pleiotropic drug-resistant sublines of human tumor cell lines. MX2 was effective ...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1991-01-01 00:00:00
abstract::Stem cells are under strict regulation by both intrinsic factors and the microenvironment. There is increasing evidence that many cancers initiate through acquisition of genetic mutations (loss of intrinsic control) in stem cells or their progenitors, followed by alterations of the surrounding microenvironment (loss o...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-10-4577
更新日期:2011-07-01 00:00:00
abstract::Lymphoid cell subpopulations infiltrating into autografts of methylcholanthrene-induced sarcomas in rats immunized with autologous tumor cells were identified in terms of immunohistochemical and cytofluorographic techniques using various monoclonal antibodies raised against different classes of rat lymphohemopoietic c...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1984-09-01 00:00:00
abstract::DNA mismatch repair (MMR) plays a key role in the cytotoxic response of human cells to methylating agents, however, the cascade of events leading to cell cycle arrest and cell death has yet to be characterized. We studied the role of MMR in the transcriptional response to DNA methylation damage in two human cellular m...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:2003-12-01 00:00:00
abstract::Myc oncoproteins exert tumorigenic effects by regulating expression of target oncogenes. Histone H3 lysine 79 (H3K79) methylation at Myc-responsive elements of target gene promoters is a strict prerequisite for Myc-induced transcriptional activation, and DOT1L is the only known histone methyltransferase that catalyzes...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-16-1663
更新日期:2017-05-01 00:00:00
abstract::Curcumin, a natural compound, is a well-known chemopreventive agent with potent anticarcinogenic activity in a wide variety of tumor cells. Curcumin inhibits cancer cell proliferation in part by suppressing cyclin D1 and inducing expression of the cyclin-dependent kinase inhibitor p21(Waf1/Cip1). Both p53-dependent an...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-07-5222
更新日期:2008-03-01 00:00:00
abstract::This report describes an early and direct action of oncogenic agents and its apparent consequences. Chemical carcinogen has been found to interact principally with a specific polypeptide in livers of normal rats. Short-term ingestion of carcinogen causes marked reductions in the concentrations of both the carcinogen:p...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1980-12-01 00:00:00
abstract::Analyses of losses of heterozygosity and linkage studies have implicated a gene(s) on chromosome 17q in the genesis of sporadic and early-onset familial breast carcinomas, respectively. To define the critical region of 17q, we examined DNAs from a series of 20 sporadic breast carcinomas and corresponding blood samples...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1992-05-01 00:00:00
abstract::In vivo studies have shown that inhibitors of cyclooxygenase metabolism of arachidonic acid may diminish growth and metastasis of certain tumors. Because cyclooxygenase inhibition may increase the production of lipoxygenase products of arachidonic acid metabolism, we have investigated the effect of two such products, ...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1985-02-01 00:00:00
abstract::Using computerized pharmacy records from 1969 to 1973 for a cohort of 143,574 members of the Kaiser Permanente Medical Care Program, we have been testing associations of 215 drugs or drug groups with subsequent incidence of cancer at 56 sites. This paper presents findings with follow-up through 1984. There were 227 st...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1989-10-15 00:00:00
abstract::Urine from 22 patients with a variety of disseminated cancers and from an equivalent number of nonmalignant controls of similar age and sex was tested for the presence of transforming growth factor (TGF) activity as measured by the ability to promote the growth in soft agar of nontransformed indicator cells. Cancer pa...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1983-01-01 00:00:00
abstract::To evaluate the role of the human T-cell-specific tyrosine kinase lck (YT16), we measured the levels of lck expression in thymocytes, peripheral T-cells, and leukemia T-cell lines which are arrested at different stages of thymic differentiation. The results indicate that higher levels of the lck message can be found i...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1988-02-15 00:00:00
abstract::Exposure to the carcinogen asbestos is a major factor in the development of malignant mesothelioma. However, not all mesotheliomas are associated with asbestos exposure, and only a small minority of people exposed to asbestos develop mesothelioma. Therefore, the identification of the cofactors that render certain indi...
journal_title:Cancer research
pub_type: 杂志文章,多中心研究
doi:
更新日期:1998-10-15 00:00:00
abstract::The structure and distribution of microfilaments were examined by electron microscopy in uninfected normal rat kidney (NRK) cells, murine sarcoma virus (MSV)-transformed NRK cells, and NRK cells infected with a cold-sensitive transformation mutant of MSV, i.e., NRK (MSV-1b) cells, grown at both permissive (39 degrees)...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1976-01-01 00:00:00
abstract::Stromal-epithelial interactions and the bioactive molecules produced by these interactions maintain tissue homeostasis and influence carcinogenesis. Bioactive prostaglandins produced by prostaglandin synthases and secreted by the prostate into seminal plasma are thought to support reproduction, but their endogenous ef...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-04-4439
更新日期:2005-07-15 00:00:00
abstract::Huggins and Morii (J. Exp. Med., 114: 741, 1961) reported that massive adrenal necrosis occurs in 79 and 100% of female Sprague-Dawley rats receiving 20 and 30 mg, respectively, of the mammary carcinogen 7,12-dimethylbenz(a)anthracene (DMBA). Here, adrenal necrosis and regeneration were studied in 158 rats for up to 2...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1988-07-01 00:00:00
abstract::The formation and persistence of O6-ethylguanine, O4-ethylthymine, and O2-ethylthymine were quantitated in the genomic DNA of human lymphoblasts exposed to 1.0 mM N-ethyl-N-nitrosourea using immunoslot-blot. The three cell lines used included one which lacks O6-alkylguanine-DNA alkyltransferase, one deficient in nucle...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1992-04-01 00:00:00
abstract::Four hr after either a single injection or continuous infusion of methotrexate (MTX) plus purified [3',5',9(n)-3H]MTX in cynomolgus or rhesus monkeys, 80 to 98% of the 3H radioactivity present in the plasma was found not to represent intact MTX. The percentage of 3H-containing MTX products in the urine after 4 hr was ...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1977-01-01 00:00:00
abstract::Analysis of ovarian carcinomas has shown that karyotypes are often highly abnormal and cannot be identified with certainty by conventional cytogenetic methods. In this study, 17 tumors derived from 13 patients were analyzed by a combination of spectral karyotyping (SKY), comparative genomic hybridization (CGH), and ex...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:2002-06-15 00:00:00
abstract::Primary and metastatic bone cancers are difficult to eradicate and novel approaches are needed to improve treatment and extend life. As bone cancer grows, osteoclasts, the principal bone-resorbing cells of the body, are recruited to and activated at sites of cancer. In this investigation, we determined if osteoclast l...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-06-1295
更新日期:2006-11-15 00:00:00
abstract::Chronic inflammation has been hypothesized to be a risk factor for prostate cancer. The Toll-like receptor 4 (TLR4) presents the bacterial lipopolysaccharide (LPS), which interacts with ligand-binding protein and CD14 (LPS receptor) and activates expression of inflammatory genes through nuclear factor-kappaB and mitog...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-05-2078
更新日期:2005-12-15 00:00:00
abstract::Alkylating agents, such as temozolomide, are among the most effective cytotoxic agents used for malignant gliomas, but responses remain very poor. The DNA repair protein O6-methylguanine-DNA methyltransferase (MGMT) plays an important role in cellular resistance to alkylating agents. IFN-beta can act as a drug sensiti...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-05-0036
更新日期:2005-09-01 00:00:00
abstract::Despite the variety of approaches used, only a limited number of tumor-associated antigens have been described for each histological type of tumor. In this report, we present a new strategy involving molecular subtraction to identify novel melanoma-associated gene sequences. Toward this end, 156 complementary DNA clon...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1991-03-01 00:00:00
abstract::Antibody-based cancer treatment depends upon distribution of the targeting macromolecule throughout tumor tissue, and spatial heterogeneity could significantly limit efficacy in many cases. Antibody distribution in tumor tissue is a function of drug dosage, antigen concentration, binding affinity, antigen internalizat...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-07-3018
更新日期:2008-05-01 00:00:00