Evidence map›Paper›PMID 30036610›Full record

ArticleCancer letters2018

mTORC2 contributes to the metabolic reprogramming in EGFR tyrosine-kinase inhibitor resistant cells in non-small cell lung cancer.

Chun-Te Chiang, Alexandra N Demetriou, Nolan Ung, Niharika Choudhury, Kimya Ghaffarian, Daniel L Ruderman, Shannon M Mumenthaler

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

Article in Cancer letters, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.

0numbers the graph read from it
0cells of the map it votes in
18citing papers in PubMed
0.8field-weighted citation impact, top 27% 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

18 citing papers in PubMed, 24 citations in OpenAlex.

  1. Review
  2. Insight into the Regulation of NDRG1 Expression.International journal of molecular sciences · 2025
    Review
  3. Review
  4. Review
  5. Phytochemicals Target Multiple Metabolic Pathways in Cancer.Antioxidants (Basel, Switzerland) · 2023
    Review
  6. Article
  7. Review
  8. Article
  9. Article
  10. Article
  11. Review
  12. Article
  13. NDRG1 in Aggressive Breast Cancer Progression and Brain Metastasis.Journal of the National Cancer Institute · 2022
    Article
  14. Review
  15. Article
  16. Review
  17. Review
  18. 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

7 authors at 1 institution in 1 country.

Chun-Te ChiangLawrence J. Ellison Institute for Transformative Medicine of USC, University of Southern California, Los Angeles, CA, USA.
Alexandra N DemetriouLawrence J. Ellison Institute for Transformative Medicine of USC, University of Southern California, Los Angeles, CA, USA.
Nolan UngLawrence J. Ellison Institute for Transformative Medicine of USC, University of Southern California, Los Angeles, CA, USA.
Niharika ChoudhuryLawrence J. Ellison Institute for Transformative Medicine of USC, University of Southern California, Los Angeles, CA, USA.
Kimya GhaffarianLawrence J. Ellison Institute for Transformative Medicine of USC, University of Southern California, Los Angeles, CA, USA.
Daniel L RudermanLawrence J. Ellison Institute for Transformative Medicine of USC, University of Southern California, Los Angeles, CA, USA.
Shannon M MumenthalerLawrence J. Ellison Institute for Transformative Medicine of USC, University of Southern California, Los Angeles, CA, USA. Electronic address: smumenth@usc.edu.
University of Southern California · US

Funding

TRANS-NETWORK PROJECTSU54CA143907 · NCI · UNIVERSITY OF SOUTHERN CALIFORNIA · PI NOLAN, GARRY P · 2009 to 2013
$15.2M
NCI NIH HHS U54 CA143907
6 · The paper itself

Abstract

Non-small cell lung cancer (NSCLC) patients with activating EGFR mutations are often successfully treated with EGFR tyrosine kinase inhibitor (TKI) such as erlotinib; however, treatment resistance inevitably occurs. Given tumor metabolism of glucose and therapeutic response are intimately linked, we explored the metabolic differences between isogenic erlotinib-sensitive and -resistant NSCLC cell lines. We discovered that the growth of erlotinib-resistant cells is more sensitive to glucose deprivation. Seahorse metabolic assay revealed erlotinib-resistant cells have lower spare respiratory capacity (SRC), an indicator of metabolic flexibility, compared to erlotinib-sensitive cells. Additionally, we found downstream components of mTORC2 signaling to be phosphorylated in erlotinib-resistant cells. Knockdown of an mTORC2 component, Rictor, enhanced the SRC and rescued the growth rate of erlotinib-resistant cells during glucose deprivation. Among NSCLCs with activating EGFR mutations, gene sets involved in glucose metabolism were enriched in patients with high expression of p-NDGR1, a readout of mTORC2 activity. Furthermore, overall survival was negatively correlated with p-NDRG1. Our work uncovers a link between mTORC2 and metabolic reprogramming in EGFR TKI-resistant cells and highlights the significance of mTORC2 in the progression of EGFR-mutated NSCLC.

Indexed as

Carcinoma, Non-Small-Cell LungCell Line, TumorCell ProliferationDrug Resistance, NeoplasmErbB ReceptorsErlotinib HydrochlorideGlucoseHumansLung NeoplasmsMechanistic Target of Rapamycin Complex 2MutationProtein Kinase InhibitorsRNA InterferenceSurvival AnalysisErbB ReceptorsErlotinib HydrochlorideGlucoseMechanistic Target of Rapamycin Complex 2Protein Kinase InhibitorsEGFR TKI resistanceGlucose metabolismmTORC2NSCLC

Identifiers

PMID30036610
PMCPMC7443389
OpenAlexW2884068068

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
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.