Evidence map›Paper›PMID 27472388›Full record

ArticleOncotarget2016

Microenvironment mediated alterations to metabolic pathways confer increased chemo-resistance in CD133+ tumor initiating cells.

Alice Nomura, Patricia Dauer, Vineet Gupta, Olivia McGinn, Nivedita Arora, Kaustav Majumdar, Charles Uhlrich, Joseph Dalluge, Vikas Dudeja, Ashok Saluja and 1 more

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

Article in Oncotarget, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.

0numbers the graph read from it
0cells of the map it votes in
36citing papers in PubMed
3.5field-weighted citation impact, top 6% 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

36 citing papers in PubMed, 59 citations in OpenAlex.

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  6. Pancreatic cancer stemness: dynamic status in malignant progression.Journal of experimental & clinical cancer research : CR · 2023
    Review
  7. Pleiotropic effects of DCLK1 in cancer and cancer stem cells.Frontiers in molecular biosciences · 2022
    Review
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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

11 authors at 3 institutions in 1 country.

Alice NomuraDivision of Basic and Translational Research, Department of Surgery, University of Minnesota, Minneapolis, MN, USA.
Patricia DauerDivision of Basic and Translational Research, Department of Surgery, University of Minnesota, Minneapolis, MN, USA.
Vineet GuptaDivision of Basic and Translational Research, Department of Surgery, University of Minnesota, Minneapolis, MN, USA.
Olivia McGinnDivision of Basic and Translational Research, Department of Surgery, University of Minnesota, Minneapolis, MN, USA.
Nivedita AroraDivision of Basic and Translational Research, Department of Surgery, University of Minnesota, Minneapolis, MN, USA.
Kaustav MajumdarDivision of Basic and Translational Research, Department of Surgery, University of Minnesota, Minneapolis, MN, USA.
Charles UhlrichDivision of Basic and Translational Research, Department of Surgery, University of Minnesota, Minneapolis, MN, USA.
Joseph DallugeDepartment of Chemistry, Mass Spectrometry Laboratory, University of Minnesota, Minneapolis, MN, USA.
Vikas DudejaDivision of Basic and Translational Research, Department of Surgery, University of Minnesota, Minneapolis, MN, USA.
Ashok SalujaDivision of Basic and Translational Research, Department of Surgery, University of Minnesota, Minneapolis, MN, USA.
Sulagna BanerjeeDivision of Basic and Translational Research, Department of Surgery, University of Minnesota, Minneapolis, MN, USA.
University of Minnesota · USUniversity of Miami · USSylvester Comprehensive Cancer Center · US

Funding

The Inhibition of HSP70 Induces Apoptosis in Pancreatic Cancer CellsR01CA124723 · NCI · UNIVERSITY OF MINNESOTA · PI GILBOA, ELI, RAMAKRISHNAN, SUNDARAM · 2007 to 2022
$4.5M
Triptolide Augments Death Receptor Mediated Apoptosis in Pancreatic CancerR01CA170946 · NCI · UNIVERSITY OF MINNESOTA · PI SALUJA, ASHOK K · 2012 to 2016
$2.4M
Functional Significance of CD133 in Pancreatic CancerR01CA184274 · NCI · UNIVERSITY OF MINNESOTA · PI BANERJEE, SULAGNA · 2014 to 2018
$1.6M
NCI NIH HHS R01 CA124723NCI NIH HHS R01 CA170946NCI NIH HHS R01 CA184274
6 · The paper itself

Abstract

Chemoresistance in pancreatic cancer has been attributed to tumor-initiating cells (TICs), a minor sub-population of tumor cells. However, the mechanism of chemo-resistance in these cells is still unclear.In the current study, immunohistochemical analysis of LSL-KrasG12D; LSL-Trp53R172H;PdxCre (KPC) murine tumors indicated that hypoxic regions developed through tumor progression. This hypoxic "niche" correlated with increased CD133+ population that had an increased HIF1A activity. Consistent with this observation, CD133+ cells had increased glucose uptake and activity of glycolytic pathway enzymes compared to CD133- cells. Mass spectrometric analysis (UPLC-TQD) following metabolic labeling of CD133+ cells with [13C]-U6 glucose confirmed this observation. Furthermore, although both populations had functionally active mitochondria, CD133+ cells had low mitochondrial complex I and complex IV activity and lesser accumulation of ROS in response to standard chemotherapeutic compounds like paclitaxel, 5FU and gemcitabine. CD133+ cells also showed increased resistance to all three chemotherapeutic compounds and treatment with Glut1 inhibitor (STF31) reversed this resistance, promoting apoptotic death in these cells similar to CD133- cells.Our study indicates that the altered metabolic profile of CD133+ pancreatic TIC protects them against apoptosis, by reducing accumulation of ROS induced by standard chemotherapeutic agents, thereby confering chemoresistance. Since resistance to existing chemotherapy contributes to the poor prognosis in pancreatic cancer, our study paves the way for identifying novel therapeutic targets for managing chemoresistance and tumor recurrence in pancreatic cancer.

Indexed as

Metabolic Networks and PathwaysTumor MicroenvironmentAC133 AntigenAnimalsAntineoplastic AgentsApoptosisCell HypoxiaCell Line, TumorCell SeparationChromatography, High Pressure LiquidDrug Resistance, NeoplasmElectron Transport Complex IElectron Transport Complex IVGlucoseGlucose Transporter Type 1HumansAC133 AntigenAntineoplastic AgentsElectron Transport Complex IElectron Transport Complex IVGlucoseGlucose Transporter Type 1Hif1a protein, mouseHypoxia-Inducible Factor 1, alpha SubunitPROM1 protein, humanProm1 protein, mouseSlc2a1 protein, mouseCD133hypoxiametabolismROStumor initiating cells

Identifiers

PMID27472388
PMCPMC5302917
OpenAlexW2477699939

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.