Related Experiment Video

Updated: Mar 12, 2026

Utilizing 18F-FDG PET/CT Imaging and Quantitative Histology to Measure Dynamic Changes in the Glucose Metabolism in Mouse Models of Lung Cancer
06:51

Utilizing 18F-FDG PET/CT Imaging and Quantitative Histology to Measure Dynamic Changes in the Glucose Metabolism in Mouse Models of Lung Cancer

Published on: July 21, 2018

18.8K

lncRNA NBR2 modulates cancer cell sensitivity to phenformin through GLUT1

Xiaowen Liu1, Boyi Gan1,2,3

  • 1a Department of Experimental Radiation Oncology , University of Texas MD Anderson Cancer Center , Houston , TS , USA.

Cell Cycle (Georgetown, Tex.)
|October 30, 2016
PubMed

Insights

Phenformin, a diabetes drug, can treat cancer. Cancer cells use NBR2 and GLUT1 to resist phenformin by affecting glucose uptake. Blocking this NBR2-GLUT1 axis may improve cancer therapy.

Area of Science:

  • Oncology
  • Molecular Biology
  • Metabolic Pathways

Background:

  • Biguanides like metformin and phenformin activate AMP-activated protein kinase (AMPK) and are explored as cancer treatments.
  • Understanding cancer cell adaptation to biguanides is crucial for developing effective cancer therapies.
  • NBR2, a long non-coding RNA (lncRNA), is induced by glucose starvation and regulates AMPK activity.

Purpose of the Study:

  • To investigate the role of NBR2 in cancer cell adaptation to phenformin treatment.
  • To elucidate the molecular mechanisms by which NBR2 influences phenformin's anti-cancer effects.
  • To identify potential therapeutic targets for enhancing biguanide-based cancer therapies.

Main Methods:

  • Phenformin treatment of cancer cells.
  • Analysis of NBR2 expression and its interaction with AMPK.
  • Assessment of glucose transporter GLUT1 expression and glucose uptake.
  • Gene depletion (siRNA) and restoration experiments.
  • Cell viability assays.

Main Results:

  • Phenformin treatment increased NBR2 expression but did not enhance its interaction with AMPK.
  • NBR2 deficiency sensitized cancer cells to phenformin-induced cell death.
  • NBR2 depletion reduced phenformin-induced GLUT1 expression and glucose uptake.
  • GLUT1 deficiency mimicked the sensitization seen with NBR2 depletion, and its restoration rescued cell death in NBR2-deficient cells.

Conclusions:

  • The NBR2-GLUT1 axis represents an adaptive response enabling cancer cells to survive phenformin treatment.
  • NBR2 promotes cancer cell survival by upregulating GLUT1 and glucose uptake under phenformin stress.
  • This study reveals a novel mechanism linking lncRNAs to biguanide-mediated cancer biology, offering potential therapeutic strategies.
Keywords:
AMPKGLUT1NBR2biguanidelong non-coding RNAphenformin

Related Concept Videos

lncRNA - Long Non-coding RNAs02:39

lncRNA - Long Non-coding RNAs

In humans, more than 80% of the genome gets transcribed. However, only around 2% of the genome codes for proteins. The remaining part produces non-coding RNAs which includes ribosomal RNAs, transfer RNAs, telomerase RNAs, and regulatory RNAs, among other types. A large number of regulatory non-coding RNAs have been classified into two groups depending upon their length – small non-coding RNAs, such as microRNA, which are less than 200 nucleotides in length, and long non-coding RNA...
10.1K
mTOR Signaling and Cancer Progression03:03

mTOR Signaling and Cancer Progression

The mammalian target of rapamycin or mTOR protein was discovered in 1994 due to its direct interaction with rapamycin. The protein gets its name from a yeast homolog called TOR. The mTOR protein complex in mammalian cells plays a major role in balancing anabolic processes such as the synthesis of proteins, lipids, and nucleotides and catabolic processes, such as autophagy in response to environmental cues, such as availability of nutrients and growth factors.
The mTOR pathway or the...
5.0K
Pharmacogenetics of Drug Targets: β₂-Adrenergic Receptors, Apo E, Thymidylate Synthase01:11

Pharmacogenetics of Drug Targets: β₂-Adrenergic Receptors, Apo E, Thymidylate Synthase

Genetic polymorphisms in drug targets have emerged as critical determinants of interindividual variability in drug response and toxicity. Pharmacogenomic investigations increasingly focus on identifying these variations to personalize and optimize therapeutic interventions. A drug target may be a receptor, enzyme, or signaling protein involved in pharmacologic responses or disease-related pathways. While early pharmacogenetic studies focused primarily on drug metabolism, current research...
61
Transducer Mechanism: Nuclear Receptors01:31

Transducer Mechanism: Nuclear Receptors

Nuclear receptors, or NRs, are unique transcription factors that regulate gene transcription and affect the cellular pathways involved in reproduction, development, or metabolism. Their ability to be stimulated by small lipophilic ligands and control vital cellular processes makes them ideal drug targets. Nearly 10-15% of currently prescribed drugs target these receptors.
About 48 different soluble family members of nuclear receptors are identified that can be divided into two main classes:
4.6K
Adaptive Mechanisms in Cancer Cells02:53

Adaptive Mechanisms in Cancer Cells

Cancer cells accumulate genetic changes at an abnormally rapid rate due to the defects in the DNA repair mechanisms. From an evolutionary perspective, such genetic instability is advantageous for cancer development. Mutant cell lines accumulate a series of beneficial mutations that contribute to their progression into cancer.
Some of the advantages that cancer cells have on normal cells include - enhanced ability to divide without terminally differentiating, induce new blood vessel formation,...
7.3K