Abstract:
:Extracellular signal-regulated kinase 1/2 (ERK1/2) constitute a point of convergence for complex signaling events that regulate essential cellular processes, including proliferation and survival. As such, dysregulation of the ERK signaling pathway is prevalent in many cancers. In the case of BRAF-V600E mutant melanoma, ERK inhibition has emerged as a viable clinical approach to abrogate signaling through the ERK pathway, even in cases where MEK and Raf inhibitor treatments fail to induce tumor regression due to resistance mechanisms. Several ERK inhibitors that target the active site of ERK have reached clinical trials, however, many critical ERK interactions occur at other potentially druggable sites on the protein. Here we discuss the role of ERK signaling in cell fate, in driving melanoma, and in resistance mechanisms to current BRAF-V600E melanoma treatments. We explore targeting ERK via a distinct site of protein-protein interaction, known as the D-recruitment site (DRS), as an alternative or supplementary mode of ERK pathway inhibition in BRAF-V600E melanoma. Targeting the DRS with inhibitors in melanoma has the potential to not only disrupt the catalytic apparatus of ERK but also its noncatalytic functions, which have significant impacts on spatiotemporal signaling dynamics and cell fate.
journal_name
Mol Carcinogjournal_title
Molecular carcinogenesisauthors
Sammons RM,Ghose R,Tsai KY,Dalby KNdoi
10.1002/mc.23047subject
Has Abstractpub_date
2019-09-01 00:00:00pages
1551-1570issue
9eissn
0899-1987issn
1098-2744journal_volume
58pub_type
杂志文章,评审abstract::An in vitro model system for xenogenization has been developed in which an immunogenic, nonmalignant phenotype was selected from a highly malignant T-cell line (S49). We showed by single-strand conformation polymorphism and DNA sequence analysis that specific point mutations in the p53 tumor suppressor gene correlated...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/mc.2940080404
更新日期:1993-01-01 00:00:00
abstract::In humans, bone marrow (BM) failure syndromes, both constitutional and acquired, predispose to myeloid malignancies. We have modeled acquired immune aplastic anemia, the paradigmatic disease of these syndromes, in the mouse by infusing lymph node cells from specific pathogen-free (SPF) CD45.1 congenic C57BL/6 (B6) don...
journal_title:Molecular carcinogenesis
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doi:10.1002/mc.23151
更新日期:2020-02-01 00:00:00
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journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/mc.1028
更新日期:2001-04-01 00:00:00
abstract::It is well known that the TP53 gene considerably influences on DNA repair processes. Polymorphisms in the TP53 gene, particularly the well-known Arg72Pro in codon 72 of exon 4 (Ex4+119 G>C; rs1042522), can modify the functionality of the p53 protein and activation of DNA repair. Actually, polymorphic variants Arg and ...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/mc.20633
更新日期:2010-06-01 00:00:00
abstract::Lasp2, as well as Lasp1, is a member of the LIM-protein subfamily of the nebulin group characterized by the combined presence of LIM and SH3 domains. Lasp1 and Lasp2 are highly conserved in their LIM, nebulin-like, and SH3 domains but differ significantly at their linker regions. Lasp1 had been described as an oncogen...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/mc.22700
更新日期:2017-12-01 00:00:00
abstract::Recently, tumor initiating cells are considered as the central role of tumorigenicity in hepatocellular carcinoma. Enediyne anticancer antibiotic lidamycin with great potential antitumor activity is currently evaluated in Phase II clinical trials. In this study, we evaluated the effect of lidamycin on tumor initiating...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/mc.22069
更新日期:2015-01-01 00:00:00
abstract::The restriction of energy intake has a profound inhibitory effect on carcinogenesis, yet the mechanism or mechanisms that account for this effect are unknown. In this experiment, the hypothesis tested was that energy restriction upregulates the expression of p27/kip1, a gene product associated with cell-cycle growth a...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/(sici)1098-2744(199904)24:4<241::aid-mc1>3
更新日期:1999-04-01 00:00:00
abstract::Resistance to cisplatin-based chemotherapy is responsible for the majority of deaths from head and neck squamous cell carcinoma (HNSCC). In this study, using genome-wide gene expression analysis to investigate potential molecular mediators of HNSCC chemoresistance, we identified SERPINB2, a known inhibitor of extracel...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/mc.22033
更新日期:2014-10-01 00:00:00
abstract::LW-213 is a derivative of Wogonin and the anticancer activities of Wogonin have been reported. To study whether LW-213 inhibits cancer cells and explore a possible mechanism, we investigate the compound in several cancer cell lines. We found LW-213 arrests G2/M cycle in breast cancer cells by suppression of Akt/Gsk3β/...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/mc.22321
更新日期:2016-05-01 00:00:00
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journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/mc.22834
更新日期:2018-09-01 00:00:00
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journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/mc.20147
更新日期:2006-01-01 00:00:00
abstract::Heterocyclic amines present in cooked foods are known to produce colon tumors in F344 rats at a high incidence, indicating the possibility of involvement of ras gene activation in colon carcinogenesis in rats as in humans. We examined mutations at codons 12, 13, and 61 of the Ki-ras, Ha-ras, and N-ras genes by polymer...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/mc.2940080110
更新日期:1993-01-01 00:00:00
abstract:UNLABELLED:Colon carcinogenesis is long known to be associated with ulcerative colitis (UC), a chronic gastrointestinal disorder. Various pre-clinical and clinical studies have shown that melatonin (MEL) has beneficial effects in cancer. However, elucidation of the detailed molecular mechanisms involved in MEL-mediated...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/mc.22274
更新日期:2016-03-01 00:00:00
abstract::Apc mutations cause intestinal tumorigenesis through Tcf4 activation. However, direct techniques for studying Tcf4 activation in vivo are limited. Here, we describe the development of a Tcf4-GFP reporter mouse model for directly studying Tcf4 activation. We first developed a GFP reporter construct (Tcf4-GFP) and trans...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/mc.20526
更新日期:2009-09-01 00:00:00
abstract::Growth factor receptors of the tyrosine kinase family regulate proliferation of a variety of cell types. In some human cancers, the epidermal growth factor receptor (EGFR) and its ligands often are overexpressed, leading to both constitutive and autocrine activation. Intracellular signaling via this receptor takes pla...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/mc.10011
更新日期:2001-12-01 00:00:00
abstract::The number of validated biomarkers of tobacco smoke exposure is limited, and none exist for tobacco-related cancer. Additional biomarkers for smoke, effects on cellular systems in vivo are needed to improve early detection of lung cancer, and to assist the Food and Drug Administration in regulating exposures to tobacc...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/mc.22385
更新日期:2016-10-01 00:00:00
abstract::Black currant fruits containing high amounts of anthocyanins are known to possess potent antioxidant and anti-inflammatory properties. We have previously reported that anthocyanin-rich black currant skin extract (BCSE) inhibits diethylnitrosamine (DENA)-initiated hepatocarcinogenesis in rats although the underlying me...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/mc.21860
更新日期:2013-04-01 00:00:00
abstract::N-acetyltransferase 1 (NAT1) is a phase II metabolic enzyme responsible for the biotransformation of aromatic and heterocyclic amine carcinogens such as 4-aminobiphenyl (ABP). NAT1 catalyzes N-acetylation of arylamines as well as the O-acetylation of N-hydroxylated arylamines. O-acetylation leads to the formation of e...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/mc.20836
更新日期:2012-08-01 00:00:00
abstract::Gastrointestinal stromal tumor (GIST) is a common mesenchymal tumor in the gastrointestinal tract. Prostate cancer associated transcript 6 (PCAT6) is a long noncoding RNA (lncRNA) and plays a pivotal role in tumor formation. Present study was designed to explore the function of PCAT6 in GIST. Ki67 staining, colony for...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/mc.23199
更新日期:2020-06-01 00:00:00
abstract::The adenovirus type 5 (Ad5) 55-kDa E1B oncoprotein has been shown to form complexes with the p53 tumor suppressor protein. These complexes are thought to interfere with normal p53 activity and may be responsible for the paucity of p53 mutations in cells transformed by these viruses. This report describes an example of...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/mc.2940120102
更新日期:1995-01-01 00:00:00
abstract::DNA hypermethylation is associated with decreased expression of tumor suppressor genes. We previously observed decreased Fhit expression and Fhit promoter region hypermethylation in rodent tumors induced by various carcinogens, and noted that the 5' regulatory regions in the promoter, exon 1, and intron 1 were differe...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/mc.20100
更新日期:2005-07-01 00:00:00
abstract::To explore the mechanisms through which hypoxic tumor microenvironment (TME) modulates the transition of tumor-associated macrophages (TAMs). The migration ability of RAW264.7 macrophages was determined by transwell assay. Flow cytometric, western blot and immunofluorescence analyses of CD206 further validated the M2 ...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/mc.22936
更新日期:2019-03-01 00:00:00
abstract::The effects of rat-specific hepatocarcinogen 3'-methyl-4-dimethylaminoazobenzene (3'-MeDAB), mouse-specific hepatocarcinogen ortho-aminoazotoluene (OAT), non-species-specific hepatocarcinogen diethylnitrosamine (DENA), and non-carcinogenic 4'-methyl-4-dimethylaminoazobenzene (4'-MeDAB) on glucocorticoid induction of t...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/mc.20090
更新日期:2005-12-01 00:00:00
abstract::The influence of the tumor promoter 2-acetylaminofluorene (2-AAF) on cell proliferation and on the epidermal growth factor receptor (EGFR) system was assessed in normal and nodular rat livers. DNA replication in vivo was inhibited below the detection level after 8d of dietary 2-AAF treatment of previously unexposed ra...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/mc.2940100207
更新日期:1994-06-01 00:00:00
abstract::Several studies have shown that E-cadherin expression is lost during malignant transformation. We hypothesized that CpG methylation in the promoter region may inactivate the expression of the E-cadherin gene in human bladder cancer. Normal and bladder cancer samples from 51 patients were compared in terms of E-cadheri...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/mc.10064
更新日期:2002-08-01 00:00:00
abstract::Dietary heterocyclic aromatic amines (HCA) and polyunsaturated fatty acids (PUFA) are both believed to play a role in colon carcinogenesis, and are both substrate for the enzyme cyclooxygenase (COX). In HCA-7 cells, highly expressing isoform COX-2, we investigated the effects of PUFA on prostaglandin synthesis and DNA...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/mc.20032
更新日期:2004-07-01 00:00:00
abstract::Xiphophorus fish have been the subject of intensive genetic research for more than 60 yr, primarily because of the availability of a number of interspecific hybrids that are malignant melanoma models with apparently simple oncogene and tumor suppressor gene determinants. The gene map of Xiphophorus is one of the most ...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/(sici)1098-2744(199807)22:3<150::aid-mc2>3
更新日期:1998-07-01 00:00:00
abstract::We have reported that connexin (Cx) 32 gene, a member of gap junction protein family, acts as a tumor suppressor gene in human renal cell carcinoma (RCC). Of solid tumors, RCC is one of the most chemoresistant cancers, and there is no effective cancer chemotherapy against RCC at present. In this study, we examined if ...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/mc.20267
更新日期:2007-03-01 00:00:00
abstract::Environmental health science research, with its focus on fundamental science and disease prevention, is important for the development of rational and cost-effective public health and regulatory policies related to environmental protection. Environmentally related diseases are preventable, yet they impose a major burde...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章,评审
doi:10.1002/mc.2940140103
更新日期:1995-09-01 00:00:00
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journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/mc.2940050307
更新日期:1992-01-01 00:00:00