Abstract:
:Breast cancer progresses in a multistep process from primary tumor growth and stroma invasion to metastasis. Nutrient-limiting environments promote chemotaxis with aggressive morphologies characteristic of invasion. It is unknown how coexisting cells differ in their response to nutrient limitations and how this impacts invasion of the metapopulation as a whole. In this study, we integrate mathematical modeling with microenvironmental perturbation data to investigate invasion in nutrient-limiting environments inhabited by one or two cancer cell subpopulations. Subpopulations were defined by their energy efficiency and chemotactic ability. Invasion distance traveled by a homogeneous population was estimated. For heterogeneous populations, results suggest that an imbalance between nutrient efficacy and chemotactic superiority accelerates invasion. Such imbalance will spatially segregate the two populations and only one type will dominate at the invasion front. Only if these two phenotypes are balanced, the two subpopulations compete for the same space, which decelerates invasion. We investigate ploidy as a candidate biomarker of this phenotypic heterogeneity and discuss its potential to inform the dose of mTOR inhibitors (mTOR-I) that can inhibit chemotaxis just enough to facilitate such competition. SIGNIFICANCE: This study identifies the double-edged sword of high ploidy as a prerequisite to personalize combination therapies with cytotoxic drugs and inhibitors of signal transduction pathways such as mTOR-Is. GRAPHICAL ABSTRACT: http://cancerres.aacrjournals.org/content/canres/80/22/5109/F1.large.jpg.
journal_name
Cancer Resjournal_title
Cancer researchauthors
Kimmel GJ,Dane M,Heiser LM,Altrock PM,Andor Ndoi
10.1158/0008-5472.CAN-20-1231subject
Has Abstractpub_date
2020-11-15 00:00:00pages
5109-5120issue
22eissn
0008-5472issn
1538-7445pii
0008-5472.CAN-20-1231journal_volume
80pub_type
杂志文章相关文献
CANCER RESEARCH文献大全abstract::Tumor necrosis factor (TNF) acts via a cell surface receptor to induce a variety of cellular events including cytolysis, differentiation, and mitogenesis. The mechanisms underlying the cell specific actions of TNF are not known. In the present study, postreceptor events associated with the autoinduction of TNF express...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1990-11-15 00:00:00
abstract::Pancreatic ductal adenocarcinoma (PDAC) is a deadly and aggressive cancer. Understanding mechanisms that drive preneoplastic pancreatic lesions is necessary to improve early diagnostic and therapeutic strategies. Mutations and inactivation of activin-like kinase (ALK4) have been demonstrated to favor PDAC onset. Surpr...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-19-3763
更新日期:2020-08-15 00:00:00
abstract::A cascade of events leading to hypertrophy has been proposed and implicated in growth regulation in a variety of normal and neoplastic cells and tissues. There is a tightly coupled temporal sequence: (a) cyclic adenosine 3':5'-monophosphate-dependent protein kinase (cAPK) activation; (b) ornithine decarboxylase (ODC) ...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1980-12-01 00:00:00
abstract::Overexpression of ABCB1 (MDR1) P-glycoprotein, a multidrug efflux pump, is one mechanism by which tumor cells may develop multidrug resistance (MDR), preventing the successful chemotherapeutic treatment of cancer. Sesquiterpenes from Celastraceae family are natural compounds shown previously to reverse MDR in several ...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-04-1005
更新日期:2004-10-01 00:00:00
abstract::Inhibition of the survival kinase Akt can trigger apoptosis, and also has been found to activate autophagy, which may confound tumor attack. In this study, we investigated regulatory mechanisms through which apoptosis and autophagy were modulated in tumor cells subjected to Akt inhibition by MK-2206, the first alloste...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-10-2889
更新日期:2011-04-01 00:00:00
abstract::Retinoids have been found to be promising chemopreventive agents that play an important role in regulating cell growth, differentiation, and apoptosis. The action of retinoids is mediated by retinoid receptors (retinoic acid receptors and retinoid X receptors), which are nuclear transcription factors that, when bound ...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-05-2515
更新日期:2006-12-15 00:00:00
abstract::Previous studies have identified RRR-alpha-tocopheryl succinate (vitamin E succinate, VES) as a potential chemotherapeutic agent. VES induces human breast cancer cells to undergo apoptosis in a concentration- and time-dependent manner by restoring transforming growth factor beta (TGF-beta) and Fas (CD95) apoptotic sig...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:2003-05-15 00:00:00
abstract::Two kinds of growth-inhibitory substances were found in culture of a Rous sarcoma virus-transformed rat liver cell line, RSV-BRL. The two substances were purified from the serum-free culture medium and identified as transforming growth factor beta 1 and Mycoplasma-derived arginine deiminase (EC 3.5.3.6), respectively....
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1990-08-01 00:00:00
abstract::Nitromidazole and nitrofuran derivatives comprise a large family of compounds, some of which have been shown to be hypoxic cell specific radiosensitizers in vivo and in vitro. The effects of metronidazole (2-methyl-5-nitroimidazole-1-ethanol) and nitrofurazone (5-nitro-2-furaldehyde semicarbazone) were studied on cell...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1976-03-01 00:00:00
abstract::The effect of microenvironmental factors on the regulation of intracellular pH (pHi) in MGH U1 cells and EMT-6 cells was studied using the fluorescent pH probe 2',7'-bis-(2-carboxyethyl)-5-(and-6)-carboxyfluorescein. Na+/H+ exchange and Na(+)-dependent Cl-/HCO3- exchange were found to be present in both cell types. Th...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1992-08-15 00:00:00
abstract::The predominant early histological changes in irradiated tissues are edema and leukocyte infiltration. Cell adhesion molecules (CAMs) are required for the extravasation of leukocytes from the circulation. To study the role of CAMs in the pathogenesis of radiation-mediated inflammation, we quantified the expression of ...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1996-11-15 00:00:00
abstract::N,N-Dimethylformamide treatment of cell cultures established from a transplantable murine rhabdomyosarcoma-induced morphological differentiation and a marked reduction in the tumorigenicity of the sarcoma cells. Fourteen of 17 CE/J mice receiving injections of inducer-treated cells did not develop tumors after 6 month...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1977-09-01 00:00:00
abstract::An anemia-inducing substance was isolated from the human placenta and designated placental anemia-inducing factor (PAIF). An amount of 2.8 mg was purified from about 70 total placentas (total wet weight, 42 kg). PAIF caused hemolysis of human erythrocytes in vitro and reduced the number of erythrocytes in rabbits to 8...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1980-05-01 00:00:00
abstract::Cells that overexpress high-mobility group A1 (HMGA1) proteins exhibit deficient nucleotide excision repair (NER) after exposure to DNA-damaging agents, a condition ameliorated by artificially lowering intracellular levels of these nonhistone proteins. One possible mechanism for this NER inhibition is down-regulation ...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-06-1689
更新日期:2007-07-01 00:00:00
abstract::Loss of expression of the apoptosis protease activator protein-1 (APAF-1) in human melanoma is thought to promote resistance to programmed cell death by preventing caspase-9 activation. However, the role of the APAF-1-dependent pathway in apoptosis activated by cellular stress and/or DNA damage has been recently quest...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-04-1640
更新日期:2004-10-15 00:00:00
abstract::Prostate cancer (PCa) is the most common male cancer in the United States. A major challenge that remains is to predict the clinical outcome in managing PCa patients. The prolyl isomerase Pin1 has been shown to be overexpressed in some human cancer tissues and thought to be an important player in several oncogenic pat...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:2003-10-01 00:00:00
abstract::Although obesity is one of the strongest risk factors for esophageal adenocarcinoma (EAC), the molecular mechanisms underlying this association remain unclear. We recently identified 4 EAC-specific master regulator transcription factors (MRTF) ELF3, KLF5, GATA6, and EHF. In the present study, Gene Set Enrichment Analy...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-20-0652
更新日期:2021-01-05 00:00:00
abstract::We have previously shown that butyrate, a short-chain fatty acid fiber fermentation product, induces colonocyte apoptosis via a nonmitochondrial, Fas-mediated, extrinsic pathway. Interestingly, fermentable fiber when combined with fish oil containing docosahexaenoic acid (DHA, 22:6n-3) exhibits an enhanced ability to ...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-06-4716
更新日期:2007-06-01 00:00:00
abstract::Retroviral and transposon-based mutagenesis screens in mice have been useful for identifying candidate cancer genes for some tumor types. However, many of the organs that exhibit the highest cancer rates in humans, including the prostate, have not previously been amenable to these approaches. This study shows for the ...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-08-3901
更新日期:2009-05-15 00:00:00
abstract::Cytidine dialdehyde inhibited the growth of leukemia L1210 cells in culture at a 50% inhibitory concentration of 3.5 X 10(-5) M and, when administered i.p. at 200 mg/kg daily for 5 days, increased the mean survival of L1210 tumor-bearing mice by up to 171%. Given by the s.c. or i.v. routes, the compound was ineffectiv...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1980-03-01 00:00:00
abstract::Interleukin 4 (IL-4) receptors were detected by a monoclonal antibody on tumor cells of 10 of 29 squamous cell carcinomas and 6 of 17 adenocarcinomas of the lung. None of the small cell carcinomas or carcinoid tumors stained. Parallel sections stained for epidermal growth factor receptors showed that all but 2 of the ...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1991-01-01 00:00:00
abstract::The gene of phosphatidylinositol 3-kinase catalytic subunit alpha (PIK3CA) has been implicated as an oncogene in ovarian cancer [L. Shayesteh et al., Nat. Genet., 21: 99-102, 1999]. In this study, we examined the expression of PIK3CA mRNA and its p110alpha protein product in human ovarian carcinoma and investigated it...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:2003-07-15 00:00:00
abstract::Although mutated forms of ras are not associated with the majority of breast cancers (<5%), there is considerable experimental evidence that hyperactive Ras can promote breast cancer growth and development. Therefore, we determined whether Ras and Ras-responsive signaling pathways were activated persistently in nine w...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-04-0396
更新日期:2004-07-01 00:00:00
abstract::Extravasation of tumor cells is a pivotal step in metastasis formation. This step is initiated by an interaction of extravasating tumor cells with endothelial cells. Among the molecules mediating tumor-endothelium interactions are selectins and their fucosylated ligands. In a previous study, we demonstrated that the f...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-03-4038
更新日期:2004-09-15 00:00:00
abstract::A two site enzyme immunoassay which quantitatively identifies types I, II, and III of protein kinase C isozymes has been designed. The soluble protein kinase C isozymes were selectively immobilized by type-specific monoclonal antibodies, MC-1a, -2a, and -3a (H. Hidaka et al., J Biol. Chem., 263: 4523-4526, 1988) which...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1990-09-01 00:00:00
abstract::Although aberrant microRNA (miRNA) is expressed in different types of human cancer tissues, its pathophysiologic role and the relevance of tumorigenesis and metastasis are still largely unknown. Here, we defined miRNAs involved in cancer metastasis (metastamirs) using an established mouse model for peritoneal dissemin...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-10-2530
更新日期:2011-02-15 00:00:00
abstract::The selective pressures leading to cancers with mutations in both KRAS and PIK3CA are unclear. Here, we show that somatic cell knockin of both KRAS G12V and oncogenic PIK3CA mutations in human breast epithelial cells results in cooperative activation of the phosphoinositide 3-kinase (PI3K) and mitogen-activated protei...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-12-1578
更新日期:2013-06-01 00:00:00
abstract::The human papillomavirus type 16 (HPV-16), the type most often associated with cervical cancer, immortalizes primary keratinocytes and inhibits serum/calcium-stimulated differentiation in culture. In this study, we have used a model of keratinocyte immortalization based upon HPV-16 to analyze perturbation of function ...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1996-11-15 00:00:00
abstract::A founder allele in the CHEK2 gene (1100delC) has been associated with an elevated risk of breast cancer. This allele is responsible for the majority of CHEK2-associated breast cancers in women from northern European countries; however, within Europe, it seems to be rare in countries that are close to the Mediterranea...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-07-5187
更新日期:2008-04-01 00:00:00
abstract::The Rb/E2F pathway is deregulated in most human brain tumors, and the finding that loss of E2F1 reduced pituitary tumorigenesis in Rb(+/-) mice suggests that loss of pRb induces brain tumors by activating E2F1. We therefore investigated the role of E2F1 in the development and maintenance of brain cancer using a transg...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-06-2973
更新日期:2007-05-01 00:00:00