Evidence map›Paper›PMID 26573582›Full record

ArticleMolecular pharmacology2016

Arsenic Attenuates GLI Signaling, Increasing or Decreasing its Transcriptional Program in a Context-Dependent Manner.

Bin Li, Camilla Giambelli, Bo Tang, Emily Winterbottom, Jun Long, Ke Jin, Zhiqiang Wang, Dennis Liang Fei, Dao M Nguyen, Mohammad Athar and 7 more

Open access · bronzeAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Molecular pharmacology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.

0numbers the graph read from it
0cells of the map it votes in
7citing papers in PubMed
0.6field-weighted citation impact, top 30% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

7 citing papers in PubMed, 9 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Review
  5. Arsenic trioxide targets MTHFD1 and SUMO-dependent nuclear de novo thymidylate biosynthesis.Proceedings of the National Academy of Sciences of the United States of America · 2017
    Article
  6. Review
  7. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

17 authors at 8 institutions in 2 countries.

Bin LiMolecular Oncology Program, Department of Surgery, Miller School of Medicine, University of Miami, Miami, Florida (B.L., C.G., E.W., J.L., K.J., Z.W., D.L.F., D.M.N., A.J.C., D.J.R.); General Surgery Center of PLA, Southwest Hospital, Third Military Medical University, Chongqing, China (B.T.); Sheila and David Fuente Graduate Program in Cancer Biology, Miller School of Medicine, University of Miami, Miami, Florida (J.L.); Program in Experimental and Molecular Medicine, Department of Pharmacology and Toxicology, Geisel School of Medicine at Dartmouth, Hanover, New Hampshire (D.L.F.); Sylvester Comprehensive Cancer Center, Miller School of Medicine, University of Miami, Miami, Florida (D.M.N., P.R.S., P.R., B.A., A.J.C., D.J.R.); Department of Dermatology, University of Alabama, Birmingham, Alabama (M.A.); Department of Genetic Medicine, Weill Medical College of Cornell University, New York, New York (B.W.); Division of Biostatistics, Department of Public Health Sciences, Miller School of Medicine, University of Miami, Miami, Florida (L. W.); Departments of Medicine (P.R.S., P.R., B.A.) and Biochemistry and Molecular Biology (A.J.C., D.J.R.), Miller School of Medicine, University of Miami, Miami, Florida; and Division of Geriatric Medicine and Palliative Care, Miller School of Medicine, University of Miami, Miami, Florida (P.R.).
Camilla GiambelliMolecular Oncology Program, Department of Surgery, Miller School of Medicine, University of Miami, Miami, Florida (B.L., C.G., E.W., J.L., K.J., Z.W., D.L.F., D.M.N., A.J.C., D.J.R.); General Surgery Center of PLA, Southwest Hospital, Third Military Medical University, Chongqing, China (B.T.); Sheila and David Fuente Graduate Program in Cancer Biology, Miller School of Medicine, University of Miami, Miami, Florida (J.L.); Program in Experimental and Molecular Medicine, Department of Pharmacology and Toxicology, Geisel School of Medicine at Dartmouth, Hanover, New Hampshire (D.L.F.); Sylvester Comprehensive Cancer Center, Miller School of Medicine, University of Miami, Miami, Florida (D.M.N., P.R.S., P.R., B.A., A.J.C., D.J.R.); Department of Dermatology, University of Alabama, Birmingham, Alabama (M.A.); Department of Genetic Medicine, Weill Medical College of Cornell University, New York, New York (B.W.); Division of Biostatistics, Department of Public Health Sciences, Miller School of Medicine, University of Miami, Miami, Florida (L. W.); Departments of Medicine (P.R.S., P.R., B.A.) and Biochemistry and Molecular Biology (A.J.C., D.J.R.), Miller School of Medicine, University of Miami, Miami, Florida; and Division of Geriatric Medicine and Palliative Care, Miller School of Medicine, University of Miami, Miami, Florida (P.R.).
Bo TangMolecular Oncology Program, Department of Surgery, Miller School of Medicine, University of Miami, Miami, Florida (B.L., C.G., E.W., J.L., K.J., Z.W., D.L.F., D.M.N., A.J.C., D.J.R.); General Surgery Center of PLA, Southwest Hospital, Third Military Medical University, Chongqing, China (B.T.); Sheila and David Fuente Graduate Program in Cancer Biology, Miller School of Medicine, University of Miami, Miami, Florida (J.L.); Program in Experimental and Molecular Medicine, Department of Pharmacology and Toxicology, Geisel School of Medicine at Dartmouth, Hanover, New Hampshire (D.L.F.); Sylvester Comprehensive Cancer Center, Miller School of Medicine, University of Miami, Miami, Florida (D.M.N., P.R.S., P.R., B.A., A.J.C., D.J.R.); Department of Dermatology, University of Alabama, Birmingham, Alabama (M.A.); Department of Genetic Medicine, Weill Medical College of Cornell University, New York, New York (B.W.); Division of Biostatistics, Department of Public Health Sciences, Miller School of Medicine, University of Miami, Miami, Florida (L. W.); Departments of Medicine (P.R.S., P.R., B.A.) and Biochemistry and Molecular Biology (A.J.C., D.J.R.), Miller School of Medicine, University of Miami, Miami, Florida; and Division of Geriatric Medicine and Palliative Care, Miller School of Medicine, University of Miami, Miami, Florida (P.R.).
Emily WinterbottomMolecular Oncology Program, Department of Surgery, Miller School of Medicine, University of Miami, Miami, Florida (B.L., C.G., E.W., J.L., K.J., Z.W., D.L.F., D.M.N., A.J.C., D.J.R.); General Surgery Center of PLA, Southwest Hospital, Third Military Medical University, Chongqing, China (B.T.); Sheila and David Fuente Graduate Program in Cancer Biology, Miller School of Medicine, University of Miami, Miami, Florida (J.L.); Program in Experimental and Molecular Medicine, Department of Pharmacology and Toxicology, Geisel School of Medicine at Dartmouth, Hanover, New Hampshire (D.L.F.); Sylvester Comprehensive Cancer Center, Miller School of Medicine, University of Miami, Miami, Florida (D.M.N., P.R.S., P.R., B.A., A.J.C., D.J.R.); Department of Dermatology, University of Alabama, Birmingham, Alabama (M.A.); Department of Genetic Medicine, Weill Medical College of Cornell University, New York, New York (B.W.); Division of Biostatistics, Department of Public Health Sciences, Miller School of Medicine, University of Miami, Miami, Florida (L. W.); Departments of Medicine (P.R.S., P.R., B.A.) and Biochemistry and Molecular Biology (A.J.C., D.J.R.), Miller School of Medicine, University of Miami, Miami, Florida; and Division of Geriatric Medicine and Palliative Care, Miller School of Medicine, University of Miami, Miami, Florida (P.R.).
Jun LongMolecular Oncology Program, Department of Surgery, Miller School of Medicine, University of Miami, Miami, Florida (B.L., C.G., E.W., J.L., K.J., Z.W., D.L.F., D.M.N., A.J.C., D.J.R.); General Surgery Center of PLA, Southwest Hospital, Third Military Medical University, Chongqing, China (B.T.); Sheila and David Fuente Graduate Program in Cancer Biology, Miller School of Medicine, University of Miami, Miami, Florida (J.L.); Program in Experimental and Molecular Medicine, Department of Pharmacology and Toxicology, Geisel School of Medicine at Dartmouth, Hanover, New Hampshire (D.L.F.); Sylvester Comprehensive Cancer Center, Miller School of Medicine, University of Miami, Miami, Florida (D.M.N., P.R.S., P.R., B.A., A.J.C., D.J.R.); Department of Dermatology, University of Alabama, Birmingham, Alabama (M.A.); Department of Genetic Medicine, Weill Medical College of Cornell University, New York, New York (B.W.); Division of Biostatistics, Department of Public Health Sciences, Miller School of Medicine, University of Miami, Miami, Florida (L. W.); Departments of Medicine (P.R.S., P.R., B.A.) and Biochemistry and Molecular Biology (A.J.C., D.J.R.), Miller School of Medicine, University of Miami, Miami, Florida; and Division of Geriatric Medicine and Palliative Care, Miller School of Medicine, University of Miami, Miami, Florida (P.R.).
Ke JinMolecular Oncology Program, Department of Surgery, Miller School of Medicine, University of Miami, Miami, Florida (B.L., C.G., E.W., J.L., K.J., Z.W., D.L.F., D.M.N., A.J.C., D.J.R.); General Surgery Center of PLA, Southwest Hospital, Third Military Medical University, Chongqing, China (B.T.); Sheila and David Fuente Graduate Program in Cancer Biology, Miller School of Medicine, University of Miami, Miami, Florida (J.L.); Program in Experimental and Molecular Medicine, Department of Pharmacology and Toxicology, Geisel School of Medicine at Dartmouth, Hanover, New Hampshire (D.L.F.); Sylvester Comprehensive Cancer Center, Miller School of Medicine, University of Miami, Miami, Florida (D.M.N., P.R.S., P.R., B.A., A.J.C., D.J.R.); Department of Dermatology, University of Alabama, Birmingham, Alabama (M.A.); Department of Genetic Medicine, Weill Medical College of Cornell University, New York, New York (B.W.); Division of Biostatistics, Department of Public Health Sciences, Miller School of Medicine, University of Miami, Miami, Florida (L. W.); Departments of Medicine (P.R.S., P.R., B.A.) and Biochemistry and Molecular Biology (A.J.C., D.J.R.), Miller School of Medicine, University of Miami, Miami, Florida; and Division of Geriatric Medicine and Palliative Care, Miller School of Medicine, University of Miami, Miami, Florida (P.R.).
Zhiqiang WangMolecular Oncology Program, Department of Surgery, Miller School of Medicine, University of Miami, Miami, Florida (B.L., C.G., E.W., J.L., K.J., Z.W., D.L.F., D.M.N., A.J.C., D.J.R.); General Surgery Center of PLA, Southwest Hospital, Third Military Medical University, Chongqing, China (B.T.); Sheila and David Fuente Graduate Program in Cancer Biology, Miller School of Medicine, University of Miami, Miami, Florida (J.L.); Program in Experimental and Molecular Medicine, Department of Pharmacology and Toxicology, Geisel School of Medicine at Dartmouth, Hanover, New Hampshire (D.L.F.); Sylvester Comprehensive Cancer Center, Miller School of Medicine, University of Miami, Miami, Florida (D.M.N., P.R.S., P.R., B.A., A.J.C., D.J.R.); Department of Dermatology, University of Alabama, Birmingham, Alabama (M.A.); Department of Genetic Medicine, Weill Medical College of Cornell University, New York, New York (B.W.); Division of Biostatistics, Department of Public Health Sciences, Miller School of Medicine, University of Miami, Miami, Florida (L. W.); Departments of Medicine (P.R.S., P.R., B.A.) and Biochemistry and Molecular Biology (A.J.C., D.J.R.), Miller School of Medicine, University of Miami, Miami, Florida; and Division of Geriatric Medicine and Palliative Care, Miller School of Medicine, University of Miami, Miami, Florida (P.R.).
Dennis Liang FeiMolecular Oncology Program, Department of Surgery, Miller School of Medicine, University of Miami, Miami, Florida (B.L., C.G., E.W., J.L., K.J., Z.W., D.L.F., D.M.N., A.J.C., D.J.R.); General Surgery Center of PLA, Southwest Hospital, Third Military Medical University, Chongqing, China (B.T.); Sheila and David Fuente Graduate Program in Cancer Biology, Miller School of Medicine, University of Miami, Miami, Florida (J.L.); Program in Experimental and Molecular Medicine, Department of Pharmacology and Toxicology, Geisel School of Medicine at Dartmouth, Hanover, New Hampshire (D.L.F.); Sylvester Comprehensive Cancer Center, Miller School of Medicine, University of Miami, Miami, Florida (D.M.N., P.R.S., P.R., B.A., A.J.C., D.J.R.); Department of Dermatology, University of Alabama, Birmingham, Alabama (M.A.); Department of Genetic Medicine, Weill Medical College of Cornell University, New York, New York (B.W.); Division of Biostatistics, Department of Public Health Sciences, Miller School of Medicine, University of Miami, Miami, Florida (L. W.); Departments of Medicine (P.R.S., P.R., B.A.) and Biochemistry and Molecular Biology (A.J.C., D.J.R.), Miller School of Medicine, University of Miami, Miami, Florida; and Division of Geriatric Medicine and Palliative Care, Miller School of Medicine, University of Miami, Miami, Florida (P.R.).
Dao M NguyenMolecular Oncology Program, Department of Surgery, Miller School of Medicine, University of Miami, Miami, Florida (B.L., C.G., E.W., J.L., K.J., Z.W., D.L.F., D.M.N., A.J.C., D.J.R.); General Surgery Center of PLA, Southwest Hospital, Third Military Medical University, Chongqing, China (B.T.); Sheila and David Fuente Graduate Program in Cancer Biology, Miller School of Medicine, University of Miami, Miami, Florida (J.L.); Program in Experimental and Molecular Medicine, Department of Pharmacology and Toxicology, Geisel School of Medicine at Dartmouth, Hanover, New Hampshire (D.L.F.); Sylvester Comprehensive Cancer Center, Miller School of Medicine, University of Miami, Miami, Florida (D.M.N., P.R.S., P.R., B.A., A.J.C., D.J.R.); Department of Dermatology, University of Alabama, Birmingham, Alabama (M.A.); Department of Genetic Medicine, Weill Medical College of Cornell University, New York, New York (B.W.); Division of Biostatistics, Department of Public Health Sciences, Miller School of Medicine, University of Miami, Miami, Florida (L. W.); Departments of Medicine (P.R.S., P.R., B.A.) and Biochemistry and Molecular Biology (A.J.C., D.J.R.), Miller School of Medicine, University of Miami, Miami, Florida; and Division of Geriatric Medicine and Palliative Care, Miller School of Medicine, University of Miami, Miami, Florida (P.R.).
Mohammad AtharMolecular Oncology Program, Department of Surgery, Miller School of Medicine, University of Miami, Miami, Florida (B.L., C.G., E.W., J.L., K.J., Z.W., D.L.F., D.M.N., A.J.C., D.J.R.); General Surgery Center of PLA, Southwest Hospital, Third Military Medical University, Chongqing, China (B.T.); Sheila and David Fuente Graduate Program in Cancer Biology, Miller School of Medicine, University of Miami, Miami, Florida (J.L.); Program in Experimental and Molecular Medicine, Department of Pharmacology and Toxicology, Geisel School of Medicine at Dartmouth, Hanover, New Hampshire (D.L.F.); Sylvester Comprehensive Cancer Center, Miller School of Medicine, University of Miami, Miami, Florida (D.M.N., P.R.S., P.R., B.A., A.J.C., D.J.R.); Department of Dermatology, University of Alabama, Birmingham, Alabama (M.A.); Department of Genetic Medicine, Weill Medical College of Cornell University, New York, New York (B.W.); Division of Biostatistics, Department of Public Health Sciences, Miller School of Medicine, University of Miami, Miami, Florida (L. W.); Departments of Medicine (P.R.S., P.R., B.A.) and Biochemistry and Molecular Biology (A.J.C., D.J.R.), Miller School of Medicine, University of Miami, Miami, Florida; and Division of Geriatric Medicine and Palliative Care, Miller School of Medicine, University of Miami, Miami, Florida (P.R.).
Baolin WangMolecular Oncology Program, Department of Surgery, Miller School of Medicine, University of Miami, Miami, Florida (B.L., C.G., E.W., J.L., K.J., Z.W., D.L.F., D.M.N., A.J.C., D.J.R.); General Surgery Center of PLA, Southwest Hospital, Third Military Medical University, Chongqing, China (B.T.); Sheila and David Fuente Graduate Program in Cancer Biology, Miller School of Medicine, University of Miami, Miami, Florida (J.L.); Program in Experimental and Molecular Medicine, Department of Pharmacology and Toxicology, Geisel School of Medicine at Dartmouth, Hanover, New Hampshire (D.L.F.); Sylvester Comprehensive Cancer Center, Miller School of Medicine, University of Miami, Miami, Florida (D.M.N., P.R.S., P.R., B.A., A.J.C., D.J.R.); Department of Dermatology, University of Alabama, Birmingham, Alabama (M.A.); Department of Genetic Medicine, Weill Medical College of Cornell University, New York, New York (B.W.); Division of Biostatistics, Department of Public Health Sciences, Miller School of Medicine, University of Miami, Miami, Florida (L. W.); Departments of Medicine (P.R.S., P.R., B.A.) and Biochemistry and Molecular Biology (A.J.C., D.J.R.), Miller School of Medicine, University of Miami, Miami, Florida; and Division of Geriatric Medicine and Palliative Care, Miller School of Medicine, University of Miami, Miami, Florida (P.R.).
Pochi R SubbarayanMolecular Oncology Program, Department of Surgery, Miller School of Medicine, University of Miami, Miami, Florida (B.L., C.G., E.W., J.L., K.J., Z.W., D.L.F., D.M.N., A.J.C., D.J.R.); General Surgery Center of PLA, Southwest Hospital, Third Military Medical University, Chongqing, China (B.T.); Sheila and David Fuente Graduate Program in Cancer Biology, Miller School of Medicine, University of Miami, Miami, Florida (J.L.); Program in Experimental and Molecular Medicine, Department of Pharmacology and Toxicology, Geisel School of Medicine at Dartmouth, Hanover, New Hampshire (D.L.F.); Sylvester Comprehensive Cancer Center, Miller School of Medicine, University of Miami, Miami, Florida (D.M.N., P.R.S., P.R., B.A., A.J.C., D.J.R.); Department of Dermatology, University of Alabama, Birmingham, Alabama (M.A.); Department of Genetic Medicine, Weill Medical College of Cornell University, New York, New York (B.W.); Division of Biostatistics, Department of Public Health Sciences, Miller School of Medicine, University of Miami, Miami, Florida (L. W.); Departments of Medicine (P.R.S., P.R., B.A.) and Biochemistry and Molecular Biology (A.J.C., D.J.R.), Miller School of Medicine, University of Miami, Miami, Florida; and Division of Geriatric Medicine and Palliative Care, Miller School of Medicine, University of Miami, Miami, Florida (P.R.).
Lily WangMolecular Oncology Program, Department of Surgery, Miller School of Medicine, University of Miami, Miami, Florida (B.L., C.G., E.W., J.L., K.J., Z.W., D.L.F., D.M.N., A.J.C., D.J.R.); General Surgery Center of PLA, Southwest Hospital, Third Military Medical University, Chongqing, China (B.T.); Sheila and David Fuente Graduate Program in Cancer Biology, Miller School of Medicine, University of Miami, Miami, Florida (J.L.); Program in Experimental and Molecular Medicine, Department of Pharmacology and Toxicology, Geisel School of Medicine at Dartmouth, Hanover, New Hampshire (D.L.F.); Sylvester Comprehensive Cancer Center, Miller School of Medicine, University of Miami, Miami, Florida (D.M.N., P.R.S., P.R., B.A., A.J.C., D.J.R.); Department of Dermatology, University of Alabama, Birmingham, Alabama (M.A.); Department of Genetic Medicine, Weill Medical College of Cornell University, New York, New York (B.W.); Division of Biostatistics, Department of Public Health Sciences, Miller School of Medicine, University of Miami, Miami, Florida (L. W.); Departments of Medicine (P.R.S., P.R., B.A.) and Biochemistry and Molecular Biology (A.J.C., D.J.R.), Miller School of Medicine, University of Miami, Miami, Florida; and Division of Geriatric Medicine and Palliative Care, Miller School of Medicine, University of Miami, Miami, Florida (P.R.).
Priyamvada RaiMolecular Oncology Program, Department of Surgery, Miller School of Medicine, University of Miami, Miami, Florida (B.L., C.G., E.W., J.L., K.J., Z.W., D.L.F., D.M.N., A.J.C., D.J.R.); General Surgery Center of PLA, Southwest Hospital, Third Military Medical University, Chongqing, China (B.T.); Sheila and David Fuente Graduate Program in Cancer Biology, Miller School of Medicine, University of Miami, Miami, Florida (J.L.); Program in Experimental and Molecular Medicine, Department of Pharmacology and Toxicology, Geisel School of Medicine at Dartmouth, Hanover, New Hampshire (D.L.F.); Sylvester Comprehensive Cancer Center, Miller School of Medicine, University of Miami, Miami, Florida (D.M.N., P.R.S., P.R., B.A., A.J.C., D.J.R.); Department of Dermatology, University of Alabama, Birmingham, Alabama (M.A.); Department of Genetic Medicine, Weill Medical College of Cornell University, New York, New York (B.W.); Division of Biostatistics, Department of Public Health Sciences, Miller School of Medicine, University of Miami, Miami, Florida (L. W.); Departments of Medicine (P.R.S., P.R., B.A.) and Biochemistry and Molecular Biology (A.J.C., D.J.R.), Miller School of Medicine, University of Miami, Miami, Florida; and Division of Geriatric Medicine and Palliative Care, Miller School of Medicine, University of Miami, Miami, Florida (P.R.).
Bach ArdalanMolecular Oncology Program, Department of Surgery, Miller School of Medicine, University of Miami, Miami, Florida (B.L., C.G., E.W., J.L., K.J., Z.W., D.L.F., D.M.N., A.J.C., D.J.R.); General Surgery Center of PLA, Southwest Hospital, Third Military Medical University, Chongqing, China (B.T.); Sheila and David Fuente Graduate Program in Cancer Biology, Miller School of Medicine, University of Miami, Miami, Florida (J.L.); Program in Experimental and Molecular Medicine, Department of Pharmacology and Toxicology, Geisel School of Medicine at Dartmouth, Hanover, New Hampshire (D.L.F.); Sylvester Comprehensive Cancer Center, Miller School of Medicine, University of Miami, Miami, Florida (D.M.N., P.R.S., P.R., B.A., A.J.C., D.J.R.); Department of Dermatology, University of Alabama, Birmingham, Alabama (M.A.); Department of Genetic Medicine, Weill Medical College of Cornell University, New York, New York (B.W.); Division of Biostatistics, Department of Public Health Sciences, Miller School of Medicine, University of Miami, Miami, Florida (L. W.); Departments of Medicine (P.R.S., P.R., B.A.) and Biochemistry and Molecular Biology (A.J.C., D.J.R.), Miller School of Medicine, University of Miami, Miami, Florida; and Division of Geriatric Medicine and Palliative Care, Miller School of Medicine, University of Miami, Miami, Florida (P.R.).
Anthony J CapobiancoMolecular Oncology Program, Department of Surgery, Miller School of Medicine, University of Miami, Miami, Florida (B.L., C.G., E.W., J.L., K.J., Z.W., D.L.F., D.M.N., A.J.C., D.J.R.); General Surgery Center of PLA, Southwest Hospital, Third Military Medical University, Chongqing, China (B.T.); Sheila and David Fuente Graduate Program in Cancer Biology, Miller School of Medicine, University of Miami, Miami, Florida (J.L.); Program in Experimental and Molecular Medicine, Department of Pharmacology and Toxicology, Geisel School of Medicine at Dartmouth, Hanover, New Hampshire (D.L.F.); Sylvester Comprehensive Cancer Center, Miller School of Medicine, University of Miami, Miami, Florida (D.M.N., P.R.S., P.R., B.A., A.J.C., D.J.R.); Department of Dermatology, University of Alabama, Birmingham, Alabama (M.A.); Department of Genetic Medicine, Weill Medical College of Cornell University, New York, New York (B.W.); Division of Biostatistics, Department of Public Health Sciences, Miller School of Medicine, University of Miami, Miami, Florida (L. W.); Departments of Medicine (P.R.S., P.R., B.A.) and Biochemistry and Molecular Biology (A.J.C., D.J.R.), Miller School of Medicine, University of Miami, Miami, Florida; and Division of Geriatric Medicine and Palliative Care, Miller School of Medicine, University of Miami, Miami, Florida (P.R.).
David J RobbinsMolecular Oncology Program, Department of Surgery, Miller School of Medicine, University of Miami, Miami, Florida (B.L., C.G., E.W., J.L., K.J., Z.W., D.L.F., D.M.N., A.J.C., D.J.R.); General Surgery Center of PLA, Southwest Hospital, Third Military Medical University, Chongqing, China (B.T.); Sheila and David Fuente Graduate Program in Cancer Biology, Miller School of Medicine, University of Miami, Miami, Florida (J.L.); Program in Experimental and Molecular Medicine, Department of Pharmacology and Toxicology, Geisel School of Medicine at Dartmouth, Hanover, New Hampshire (D.L.F.); Sylvester Comprehensive Cancer Center, Miller School of Medicine, University of Miami, Miami, Florida (D.M.N., P.R.S., P.R., B.A., A.J.C., D.J.R.); Department of Dermatology, University of Alabama, Birmingham, Alabama (M.A.); Department of Genetic Medicine, Weill Medical College of Cornell University, New York, New York (B.W.); Division of Biostatistics, Department of Public Health Sciences, Miller School of Medicine, University of Miami, Miami, Florida (L. W.); Departments of Medicine (P.R.S., P.R., B.A.) and Biochemistry and Molecular Biology (A.J.C., D.J.R.), Miller School of Medicine, University of Miami, Miami, Florida; and Division of Geriatric Medicine and Palliative Care, Miller School of Medicine, University of Miami, Miami, Florida (P.R.) drobbins@med.miami.edu.
Sylvester Comprehensive Cancer Center · USUniversity of Alabama at Birmingham · USCornell University · USDartmouth College · USSouthwest Hospital · CNUniversity of Miami · USArmy Medical University · CNMolecular Oncology (United States) · US

Funding

Project 3: Placental Biomarkers of Exposure and Outcome (Marsit)P01ES022832 · NIEHS · DARTMOUTH COLLEGE · PI MURRAY, CAROLYN J · 2013 to 2018
$4.7M
Characterization of Sonic Hedgehog BiogenesisR01GM064011 · NIGMS · UNIVERSITY OF MIAMI SCHOOL OF MEDICINE · PI ROBBINS, DAVID J · 2002 to 2011
$2.6M
The role of Dzip1L in ciliogenesis and Hedgehog signalingR01GM114429 · NIGMS · WEILL MEDICAL COLL OF CORNELL UNIV · PI WANG, BAOLIN · 2015 to 2018
$1.4M
Reversal of 5-FU Resistance by Arsenic Trioxide in Colorectal CarcinomaR21CA117116 · NCI · UNIVERSITY OF MIAMI SCHOOL OF MEDICINE · PI ARDALAN, BACH · 2007 to 2008
$581k
Characterization of Sonic Hedgehog BiogenesisR56GM064011 · NIGMS · DARTMOUTH COLLEGE · PI ROBBINS, DAVID J · 2007 to 2007
$327k
NCI NIH HHS 1R21CA117116-01NCI NIH HHS R21 CA117116NIEHS NIH HHS P01ES01817502NIEHS NIH HHS P01 ES022832NIGMS NIH HHS GM64011NIGMS NIH HHS R01 GM064011NIGMS NIH HHS R01 GM114429NIGMS NIH HHS R56 GM064011
6 · The paper itself

Abstract

The metalloid arsenic is a worldwide environmental toxicant, exposure to which is associated with many adverse outcomes. Arsenic is also an effective therapeutic agent in certain disease settings. Arsenic was recently shown to regulate the activity of the Hedgehog (HH) signal transduction pathway, and this regulation of HH signaling was proposed to be responsible for a subset of arsenic's biologic effects. Surprisingly, these separate reports proposed contradictory activities for arsenic, as either an agonist or antagonist of HH signaling. Here we provide in vitro and in vivo evidence that arsenic acts as a modulator of the activity of the HH effector protein glioma-associated oncogene family zinc finger (GLI), activating or inhibiting GLI activity in a context-dependent manner. This arsenic-induced modulation of HH signaling is observed in cultured cells, patients with colorectal cancer who have received arsenic-based therapy, and a mouse colorectal cancer xenograft model. Our results show that arsenic activates GLI signaling when the intrinsic GLI activity is low but inhibits signaling in the presence of high-level GLI activity. Furthermore, we show that this modulation occurs downstream of primary cilia, evidenced by experiments in suppressor of fused homolog (SUFU) deficient cells. Combining our findings with previous reports, we present an inclusive model in which arsenic plays dual roles in GLI signaling modulation: when GLIs are primarily in their repressor form, arsenic antagonizes their repression capacity, leading to low-level GLI activation, but when GLIs are primarily in their activator form, arsenic attenuates their activity.

Indexed as

AnimalsArsenicFemaleHCT116 CellsHumansMiceMice, NudeNIH 3T3 CellsSignal TransductionTranscription FactorsTranscription, GeneticXenograft Model Antitumor AssaysZinc Finger Protein GLI1ArsenicGLI1 protein, humanTranscription FactorsZinc Finger Protein GLI1

Identifiers

PMID26573582
PMCPMC4727125
OpenAlexW2285670684

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