当前位置： SCI文献检索 > PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA期刊下所有文献 > Metformin selectively inhibits metastatic colorectal cancer with the KRAS mutation by intracellular accumulation through silencing MATE1.

Metformin selectively inhibits metastatic colorectal cancer with the KRAS mutation by intracellular accumulation through silencing MATE1.

Abstract：

:Metastatic colorectal cancer (mCRC) patients have poor overall survival despite using irinotecan- or oxaliplatin-based chemotherapy combined with anti-EGFR (epidermal growth factor receptor) drugs, especially those with the oncogene mutation of KRAS Metformin has been reported as a potentially novel antitumor agent in many experiments, but its therapeutic activity is discrepant and controversial so far. Inspiringly, the median survival time for KRAS-mutation mCRC patients with diabetes on metformin is 37.8 mo longer than those treated with other hypoglycemic drugs in combination with standard systemic therapy. In contrast, metformin could not improve the survival of mCRC patients with wild-type KRAS Interestingly, metformin is preferentially accumulated in KRAS-mutation mCRC cells, but not wild-type ones, in both primary cell cultures and patient-derived xenografts, which is in agreement with its tremendous effect in KRAS-mutation mCRC. Mechanistically, the mutated KRAS oncoprotein hypermethylates and silences the expression of multidrug and toxic compound extrusion 1 (MATE1), a specific pump that expels metformin from the tumor cells by up-regulating DNA methyltransferase 1 (DNMT1). Our findings provide evidence that KRAS-mutation mCRC patients benefit from metformin treatment and targeting MATE1 may provide a strategy to improve the anticancer response of metformin.

journal_name

Proc Natl Acad Sci U S A

journal_title

Proceedings of the National Academy of Sciences of the United States of America

authors

Xie J,Xia L,Xiang W,He W,Yin H,Wang F,Gao T,Qi W,Yang Z,Yang X,Zhou T,Gao G

doi

10.1073/pnas.1918845117

subject

Has Abstract

pub_date

2020-06-09 00:00:00

pages

13012-13022

issue

23

eissn

0027-8424

issn

1091-6490

pii

1918845117

journal_volume

117

pub_type

杂志文章

相关文献

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA文献大全
  • Mutational landscape of uterine and ovarian carcinosarcomas implicates histone genes in epithelial-mesenchymal transition.

    abstract：:Carcinosarcomas (CSs) of the uterus and ovary are highly aggressive neoplasms containing both carcinomatous and sarcomatous elements. We analyzed the mutational landscape of 68 uterine and ovarian CSs by whole-exome sequencing. We also performed multiregion whole-exome sequencing comprising two carcinoma and sarcoma s...

    journal_title：Proceedings of the National Academy of Sciences of the United States of America

    pub_type： 杂志文章

    doi：10.1073/pnas.1614120113

    authors： Zhao S,Bellone S,Lopez S,Thakral D,Schwab C,English DP,Black J,Cocco E,Choi J,Zammataro L,Predolini F,Bonazzoli E,Bi M,Buza N,Hui P,Wong S,Abu-Khalaf M,Ravaggi A,Bignotti E,Bandiera E,Romani C,Todeschini P,Tas

    更新日期：2016-10-25 00:00:00

  • GABA exerts protective and regenerative effects on islet beta cells and reverses diabetes.

    abstract：:Type 1 diabetes (T1D) is an autoimmune disease characterized by insulitis and islet β-cell loss. Thus, an effective therapy may require β-cell restoration and immune suppression. Currently, there is no treatment that can achieve both goals efficiently. We report here that GABA exerts antidiabetic effects by acting on ...

    journal_title：Proceedings of the National Academy of Sciences of the United States of America

    pub_type： 杂志文章

    doi：10.1073/pnas.1102715108

    authors： Soltani N,Qiu H,Aleksic M,Glinka Y,Zhao F,Liu R,Li Y,Zhang N,Chakrabarti R,Ng T,Jin T,Zhang H,Lu WY,Feng ZP,Prud'homme GJ,Wang Q

    更新日期：2011-07-12 00:00:00

  • Theory of a class of locally convex vector lattices which include the lebesgue spaces.

    abstract：:In this paper is presented the theory of a class of locally convex lattices (L-lattices) of real functions which generalize the classical Lebesgue spaces. The monotone and dominated convergence theorems for convergence almost everywhere and sequential and order completeness of such lattices are established. These resu...

    journal_title：Proceedings of the National Academy of Sciences of the United States of America

    pub_type： 杂志文章

    doi：10.1073/pnas.66.2.275

    authors： Bogdanowicz WM

    更新日期：1970-06-01 00:00:00

  • Introduction of plasmid DNA into the trypanosomatid protozoan Crithidia fasciculata.

    abstract：:Crithidia fasciculata cells were treated with a plasmid (pDK96) containing pBR322 sequences, a Leishmania tarentolae maxicircle autonomously replicating sequence, and the bacterial gene for aminoglycoside 3' phosphotransferase I inserted between the yeast alcohol dehydrogenase 1 promotor and terminator sequences. Resi...

    journal_title：Proceedings of the National Academy of Sciences of the United States of America

    pub_type： 杂志文章

    doi：10.1073/pnas.83.16.6058

    authors： Hughes DE,Simpson L

    更新日期：1986-08-01 00:00:00

  • Differential effects of ethanol antagonism and neuroprotection in peptide fragment NAPVSIPQ prevention of ethanol-induced developmental toxicity.

    abstract：:NAPVSIPQ (NAP), an active fragment of the glial-derived activity-dependent neuroprotective protein, is protective at femtomolar concentrations against a wide array of neural insults and prevents ethanol-induced fetal wastage and growth retardation in mice. NAP also antagonizes ethanol inhibition of L1-mediated cell ad...

    journal_title：Proceedings of the National Academy of Sciences of the United States of America

    pub_type： 杂志文章

    doi：10.1073/pnas.1331636100

    authors： Wilkemeyer MF,Chen SY,Menkari CE,Brenneman DE,Sulik KK,Charness ME

    更新日期：2003-07-08 00:00:00

  • Biomechanical activation of vascular endothelium as a determinant of its functional phenotype.

    abstract：:One of the striking features of vascular endothelium, the single-cell-thick lining of the cardiovascular system, is its phenotypic plasticity. Various pathophysiologic factors, such as cytokines, growth factors, hormones, and metabolic products, can modulate its functional phenotype in health and disease. In addition ...

    journal_title：Proceedings of the National Academy of Sciences of the United States of America

    pub_type： 杂志文章

    doi：10.1073/pnas.071052598

    authors： Garcia-Cardeña G,Comander J,Anderson KR,Blackman BR,Gimbrone MA Jr

    更新日期：2001-04-10 00:00:00

  • Multiple pathways in pressure-induced phase transition of coesite.

    abstract：:High-pressure single-crystal X-ray diffraction method with precise control of hydrostatic conditions, typically with helium or neon as the pressure-transmitting medium, has significantly changed our view on what happens with low-density silica phases under pressure. Coesite is a prototype material for pressure-induced...

    journal_title：Proceedings of the National Academy of Sciences of the United States of America

    pub_type： 杂志文章

    doi：10.1073/pnas.1710651114

    authors： Liu W,Wu X,Liang Y,Liu C,Miranda CR,Scandolo S

    更新日期：2017-12-05 00:00:00

  • SK channels mediate NADPH oxidase-independent reactive oxygen species production and apoptosis in granulocytes.

    abstract：:Neutrophils are immune cells that bind to, engulf, and destroy bacterial and fungal pathogens in infected tissue, and their clearance by apoptosis is essential for the resolution of inflammation. Killing involves both oxidative and nonoxidative processes, the oxidative pathway requiring electrogenic production of supe...

    journal_title：Proceedings of the National Academy of Sciences of the United States of America

    pub_type： 杂志文章

    doi：10.1073/pnas.0607914103

    authors： Fay AJ,Qian X,Jan YN,Jan LY

    更新日期：2006-11-14 00:00:00

  • Coevolution of landesque capital intensive agriculture and sociopolitical hierarchy.

    abstract：:One of the defining trends of the Holocene has been the emergence of complex societies. Two essential features of complex societies are intensive resource use and sociopolitical hierarchy. Although it is widely agreed that these two phenomena are associated cross-culturally and have both contributed to the rise of com...

    journal_title：Proceedings of the National Academy of Sciences of the United States of America

    pub_type： 杂志文章

    doi：10.1073/pnas.1714558115

    authors： Sheehan O,Watts J,Gray RD,Atkinson QD

    更新日期：2018-04-03 00:00:00

  • Global environmental impacts of agricultural expansion: the need for sustainable and efficient practices.

    abstract：:The recent intensification of agriculture, and the prospects of future intensification, will have major detrimental impacts on the nonagricultural terrestrial and aquatic ecosystems of the world. The doubling of agricultural food production during the past 35 years was associated with a 6.87-fold increase in nitrogen ...

    journal_title：Proceedings of the National Academy of Sciences of the United States of America

    pub_type： 杂志文章

    doi：10.1073/pnas.96.11.5995

    authors： Tilman D

    更新日期：1999-05-25 00:00:00

  • Nociceptin/orphanin FQ-induced nociceptive responses through substance P release from peripheral nerve endings in mice.

    abstract：:We have studied the in vivo signaling mechanisms involved in nociceptin/orphanin FQ (Noci)-induced pain responses by using a flexor-reflex paradigm. Noci was 10,000 times more potent than substance P (SP) in eliciting flexor responses after intraplantar injection into the hind limb of mice, but the action of Noci seem...

    journal_title：Proceedings of the National Academy of Sciences of the United States of America

    pub_type： 杂志文章

    doi：10.1073/pnas.95.18.10949

    authors： Inoue M,Kobayashi M,Kozaki S,Zimmer A,Ueda H

    更新日期：1998-09-01 00:00:00

  • Reduced cGMP signaling associated with neointimal proliferation and vascular dysfunction in late-stage atherosclerosis.

    abstract：:Atherosclerosis is associated with alterations in nitric oxide (NO)/cGMP signaling. In early stages of the disease, inflammatory and possibly other cells produce reactive oxygen species that scavenge vasoprotective NO. In addition to the oxidative stress, expression and activity of enzymes downstream to NO formation m...

    journal_title：Proceedings of the National Academy of Sciences of the United States of America

    pub_type： 杂志文章

    doi：10.1073/pnas.0405509101

    authors： Melichar VO,Behr-Roussel D,Zabel U,Uttenthal LO,Rodrigo J,Rupin A,Verbeuren TJ,Kumar H S A,Schmidt HH

    更新日期：2004-11-23 00:00:00

  • Growth of transplanted tails of infant rats in adolescent allogeneic recipients.

    abstract：:The tails of newborn rats, consisting of slender continuous cones of avascular cartilage, were transplanted in subcutaneous spaces of allogeneic adolescents; colloidal carbon was injected in a vein before the transplants were harvested on days 7-28. Between 97 and 100% of the transplants were accepted, underwent diffe...

    journal_title：Proceedings of the National Academy of Sciences of the United States of America

    pub_type： 杂志文章

    doi：10.1073/pnas.73.9.3283

    authors： Huggins CB,Anderson KP

    更新日期：1976-09-01 00:00:00

  • Yeast calmodulin and a conserved nuclear protein participate in the in vivo binding of a matrix association region.

    abstract：:Chromatin becomes reorganized during mitosis each cell cycle. To identify genes potentially involved in these supramolecular events, we have used a colony-color assay to screen temperature-sensitive mutants of Saccharomyces cerevisiae. When a sequence that mediates attachment to the nuclear matrix in vitro was inserte...

    journal_title：Proceedings of the National Academy of Sciences of the United States of America

    pub_type： 杂志文章

    doi：10.1073/pnas.90.12.5623

    authors： Fishel BR,Sperry AO,Garrard WT

    更新日期：1993-06-15 00:00:00

  • IL-17 production from activated T cells is required for the spontaneous development of destructive arthritis in mice deficient in IL-1 receptor antagonist.

    abstract：:IL-17 is a T cell-derived, proinflammatory cytokine that is suspected to be involved in the development of various inflammatory diseases. Although there are elevated levels of IL-17 in synovial fluid of patients with rheumatoid arthritis, the pathogenic role of IL-17 in the development of rheumatoid arthritis remains ...

    journal_title：Proceedings of the National Academy of Sciences of the United States of America

    pub_type： 杂志文章

    doi：10.1073/pnas.1035999100

    authors： Nakae S,Saijo S,Horai R,Sudo K,Mori S,Iwakura Y

    更新日期：2003-05-13 00:00:00

  • Purification of a galanin receptor from pig brain.

    abstract：:A galanin receptor protein was solubilized with 3-[(3-cholamidopropyl)dimethylammonio]-1-propanesulfonate (CHAPS) from pig brain membranes and then purified by single-step affinity chromatography. The product exhibits saturable and specific binding for galanin with a binding activity of 17 nmol/mg of protein and a dis...

    journal_title：Proceedings of the National Academy of Sciences of the United States of America

    pub_type： 杂志文章

    doi：10.1073/pnas.90.9.3845

    authors： Chen Y,Fournier A,Couvineau A,Laburthe M,Amiranoff B

    更新日期：1993-05-01 00:00:00

  • Confocal light absorption and scattering spectroscopic microscopy monitors organelles in live cells with no exogenous labels.

    abstract：:This article reports the development of an optical imaging technique, confocal light absorption and scattering spectroscopic (CLASS) microscopy, capable of noninvasively determining the dimensions and other physical properties of single subcellular organelles. CLASS microscopy combines the principles of light-scatteri...

    journal_title：Proceedings of the National Academy of Sciences of the United States of America

    pub_type： 杂志文章

    doi：10.1073/pnas.0708669104

    authors： Itzkan I,Qiu L,Fang H,Zaman MM,Vitkin E,Ghiran IC,Salahuddin S,Modell M,Andersson C,Kimerer LM,Cipolloni PB,Lim KH,Freedman SD,Bigio I,Sachs BP,Hanlon EB,Perelman LT

    更新日期：2007-10-30 00:00:00

  • Linguistic threat activates the human amygdala.

    abstract：:Studies in animals demonstrate a crucial role for the amygdala in emotional and social behavior, especially as related to fear and aggression. Whereas lesion and functional-imaging studies in humans indicate the amygdala's participation in assessing the significance of nonverbal as well as paralinguistic cues, direct ...

    journal_title：Proceedings of the National Academy of Sciences of the United States of America

    pub_type： 杂志文章

    doi：10.1073/pnas.96.18.10456

    authors： Isenberg N,Silbersweig D,Engelien A,Emmerich S,Malavade K,Beattie B,Leon AC,Stern E

    更新日期：1999-08-31 00:00:00

  • Differences in spontaneous mutation frequencies as a function of environmental stress in soil fungi at "Evolution Canyon," Israel.

    abstract：:When various wild strains of Penicillium lanosum and Aspergillus niger were placed in the same mild laboratory environment, their frequencies of new spontaneous mutations were clearly related to whether they had been isolated from a region of high or low microclimatic stress. In the mild environment, the total frequen...

    journal_title：Proceedings of the National Academy of Sciences of the United States of America

    pub_type： 杂志文章

    doi：10.1073/pnas.0801995105

    authors： Lamb BC,Mandaokar S,Bahsoun B,Grishkan I,Nevo E

    更新日期：2008-04-15 00:00:00

  • High-seas fish wars generate marine reserves.

    abstract：:The effective management of marine fisheries is an ongoing challenge at the intersection of biology, economics, and policy. One way in which fish stocks-and their habitats-can be protected is through the establishment of marine reserves, areas that are closed to fishing. Although the potential economic benefits of suc...

    journal_title：Proceedings of the National Academy of Sciences of the United States of America

    pub_type： 杂志文章

    doi：10.1073/pnas.1518509113

    authors： Herrera GE,Moeller HV,Neubert MG

    更新日期：2016-04-05 00:00:00

  • Structure, function, and self-assembly of single network gyroid (I4132) photonic crystals in butterfly wing scales.

    abstract：:Complex three-dimensional biophotonic nanostructures produce the vivid structural colors of many butterfly wing scales, but their exact nanoscale organization is uncertain. We used small angle X-ray scattering (SAXS) on single scales to characterize the 3D photonic nanostructures of five butterfly species from two fam...

    journal_title：Proceedings of the National Academy of Sciences of the United States of America

    pub_type： 杂志文章

    doi：10.1073/pnas.0909616107

    authors： Saranathan V,Osuji CO,Mochrie SG,Noh H,Narayanan S,Sandy A,Dufresne ER,Prum RO

    更新日期：2010-06-29 00:00:00

  • Intramembrane charge movements and excitation- contraction coupling expressed by two-domain fragments of the Ca2+ channel.

    abstract：:To investigate the molecular basis of the voltage sensor that triggers excitation-contraction (EC) coupling, the four-domain pore subunit of the dihydropyridine receptor (DHPR) was cut in the cytoplasmic linker between domains II and III. cDNAs for the I-II domain (alpha1S 1-670) and the III-IV domain (alpha1S 701-187...

    journal_title：Proceedings of the National Academy of Sciences of the United States of America

    pub_type： 杂志文章

    doi：10.1073/pnas.111001898

    authors： Ahern CA,Arikkath J,Vallejo P,Gurnett CA,Powers PA,Campbell KP,Coronado R

    更新日期：2001-06-05 00:00:00

  • Expression of tobacco mosaic virus coat protein and assembly of pseudovirus particles in Escherichia coli.

    abstract：:The bidirectional self-assembly of tobacco mosaic virus (TMV, common or U1 strain) has been studied extensively in vitro. Foreign single-stranded RNA molecules containing the TMV origin-of-assembly sequence (OAS, 75-432 nt in length) are also packaged by TMV coat protein (CP) in vitro to form helical pseudovirus parti...

    journal_title：Proceedings of the National Academy of Sciences of the United States of America

    pub_type： 杂志文章

    doi：10.1073/pnas.91.19.9067

    authors： Hwang DJ,Roberts IM,Wilson TM

    更新日期：1994-09-13 00:00:00

  • DNA length, bending, and twisting constraints on IS50 transposition.

    abstract：:Transposition is a multistep process in which a transposable element DNA sequence moves from its original genetic location to a new site. Early steps in this process include the formation of a transposition complex in which the end sequences of the transposable element are brought together in a structurally precise fa...

    journal_title：Proceedings of the National Academy of Sciences of the United States of America

    pub_type： 杂志文章

    doi：10.1073/pnas.91.23.10834

    authors： Goryshin IYu,Kil YV,Reznikoff WS

    更新日期：1994-11-08 00:00:00

  • Cloning of a human complement component C4 gene.

    abstract：:Six overlapping cosmid clones having an average insert size of 40 kilobase pairs were identified and isolated from a human genomic library by using a cDNA probe, Alu-7, specific for the amino acid sequence of C4d, a known region of the fourth component of human complement. Analysis of these genomic clones by restricti...

    journal_title：Proceedings of the National Academy of Sciences of the United States of America

    pub_type： 杂志文章

    doi：10.1073/pnas.80.1.264

    authors： Carroll MC,Porter RR

    更新日期：1983-01-01 00:00:00

  • Nucleotide sequence of the ampicillin resistance gene of Escherichia coli plasmid pBR322.

    abstract：:I have determined the nucleotide sequence of the ampicillin resistance gene of pBR322, an Escherichia coli plasmid that encodes a penicillin beta-lactamase. This gene codes for a protein of 286 amino acid residues. The first 23 amino acids presumably form a signal for secretion, because they do not appear in the matur...

    journal_title：Proceedings of the National Academy of Sciences of the United States of America

    pub_type： 杂志文章

    doi：10.1073/pnas.75.8.3737

    authors： Sutcliffe JG

    更新日期：1978-08-01 00:00:00

  • Enzyme assay in microsomes below zero degrees.

    abstract：:Reactions of a membrane-bound multienzyme complex (electron-transport chain of rat-liver microsomes) suspended in aqueous-organic solvent used as antifreeze at temperatures below 0 degrees were studied. In the presence of a relatively high concentration of ethylene glycol, electron transfer can still be observed and s...

    journal_title：Proceedings of the National Academy of Sciences of the United States of America

    pub_type： 杂志文章

    doi：10.1073/pnas.70.9.2633

    authors： Debey P,Balny C,Douzou P

    更新日期：1973-09-01 00:00:00

  • Altered pharmacology and distinct coactivator usage for estrogen receptor-dependent transcription through activating protein-1.

    abstract：:Estrogen signaling occurs through at least two distinct molecular pathways: (i) direct binding of liganded estrogen receptors (ERs) to estrogen-responsive DNA elements (EREs) (the "ER/ERE pathway") and (ii) indirect recruitment of liganded ERs to activating protein-1 (AP-1)-responsive DNA elements via heterodimers of ...

    journal_title：Proceedings of the National Academy of Sciences of the United States of America

    pub_type： 杂志文章

    doi：10.1073/pnas.0407113102

    authors： Cheung E,Acevedo ML,Cole PA,Kraus WL

    更新日期：2005-01-18 00:00:00

  • A parallelized, automated platform enabling individual or sequential ChIP of histone marks and transcription factors.

    abstract：:Despite its popularity, chromatin immunoprecipitation followed by sequencing (ChIP-seq) remains a tedious (>2 d), manually intensive, low-sensitivity and low-throughput approach. Here, we combine principles of microengineering, surface chemistry, and molecular biology to address the major limitations of standard ChIP-...

    journal_title：Proceedings of the National Academy of Sciences of the United States of America

    pub_type： 杂志文章

    doi：10.1073/pnas.1913261117

    authors： Dainese R,Gardeux V,Llimos G,Alpern D,Jiang JY,Meireles-Filho ACA,Deplancke B

    更新日期：2020-06-16 00:00:00

  • SRY recognizes conserved DNA sites in sex-specific promoters.

    abstract：:Formation of male-specific structures and regression of female primordia are regulated in early male embryogenesis by SRY, a single-copy gene on the Y chromosome. Assignment of SRY as the testis-determining factor in eutherian mammals is supported by molecular analysis of cytogenetic sex reversal (i.e., XX males and X...

    journal_title：Proceedings of the National Academy of Sciences of the United States of America

    pub_type： 杂志文章

    doi：10.1073/pnas.90.3.1097

    authors： Haqq CM,King CY,Donahoe PK,Weiss MA

    更新日期：1993-02-01 00:00:00