Related Experiment Video

Updated: Jan 28, 2026

Radiosensitivity of Cancer Stem Cells in Lung Cancer Cell Lines
09:45

Radiosensitivity of Cancer Stem Cells in Lung Cancer Cell Lines

Published on: August 21, 2019

7.5K

FGF2-FGFR1 pathway activation together with thymidylate synthase upregulation is induced in pemetrexed-resistant lung

Kentaro Miura1, Takaaki Oba1, Kazutoshi Hamanaka1

  • 1Division of Breast, Endocrine and Respiratory Surgery, Department of Surgery (II), Shinshu University School of Medicine, Matsumoto, Japan.

Oncotarget
|March 7, 2019
PubMed

Insights

This study reveals the fibroblast growth factor 2 (FGF2) and FGF receptor 1 (FGFR1) pathway contributes to pemetrexed resistance in non-small cell lung cancer. Inhibiting this pathway can restore sensitivity, highlighting a potential therapeutic target.

Area of Science:

  • Molecular Biology
  • Oncology
  • Cancer Research

Background:

  • Pemetrexed (MTA) is a key antifolate drug for non-small cell lung cancer (NSCLC).
  • Mechanisms of pemetrexed resistance in NSCLC remain incompletely understood.
  • Understanding resistance is crucial for improving treatment efficacy.

Purpose of the Study:

  • To investigate the molecular mechanisms underlying pemetrexed resistance in NSCLC.
  • To identify novel pathways involved in pemetrexed resistance.
  • To explore potential therapeutic strategies targeting these pathways.

Main Methods:

  • Establishment of pemetrexed-resistant NSCLC cell lines (PC9-MTA, H1993-MTA).
  • Microarray analysis for gene expression profiling.
  • Confirmation of gene and protein expression using Western blotting, ELISA, and RT-PCR.
  • Functional studies involving siRNA-mediated knockdown and pharmacological inhibition (PD173074).

Main Results:

  • Enhanced expression of fibroblast growth factor 2 (FGF2) and FGF receptor 1 (FGFR1) was observed in resistant cell lines.
  • FGF2/FGFR1 inhibition partially restored pemetrexed sensitivity.
  • Specific effects on ERK phosphorylation and epithelial-mesenchymal transition (EMT) markers were cell-line dependent.
  • FGF2/FGFR1 pathway activation influences cell-specific alterations contributing to resistance.

Conclusions:

  • The FGF2-FGFR1 signaling pathway plays a significant role in mediating pemetrexed resistance in NSCLC.
  • Targeting the FGF2-FGFR1 pathway presents a potential strategy to overcome pemetrexed resistance.
  • The impact of FGF2-FGFR1 pathway activation on resistance mechanisms is influenced by intrinsic cancer cell characteristics.
Keywords:
FGFR pathwaydrug resistanceepithelial-mesenchymal transitionlung cancerpemetrexed

More Related Videos

A Colorimetric Assay of Citrate Synthase Activity in Drosophila Melanogaster04:30

A Colorimetric Assay of Citrate Synthase Activity in Drosophila Melanogaster

Published on: January 16, 2020

10.7K
Detection of Targetable Alterations in Non-small Cell Lung Cancer using Next-generation Sequencing05:17

Detection of Targetable Alterations in Non-small Cell Lung Cancer using Next-generation Sequencing

Published on: October 10, 2025

379

Related Concept Videos

Treatment Resistant Cancers02:56

Treatment Resistant Cancers

Cancer is the second leading cause of death in the United States. A cancer cell is genetically unstable and hence can mutate faster. They can also modify their microenvironment and escape immune surveillance. The difficulties in treating cancer are further compounded by the emergence of rapid resistance to anticancer drugs. The most common ways to attain resistance in cancer cells include alteration in drug transport and metabolism, modification of drug target, elevated DNA damage response, or...
3.7K
ATP Synthase: Mechanism01:48

ATP Synthase: Mechanism

In animals, the mitochondrial F1F0 ATP synthase is the key protein that synthesizes ATP molecules through a complex catalytic mechanism. While the nuclear genome encodes the majority of ATP synthase subunits, the mitochondrial genome encodes some of the enzyme's most critical components. The formation of this multi-subunit enzyme is a complex multi-step process regulated at the level of transcription, translation, and assembly. Defects in one or more of these steps can result in decreased...
17.0K
ATP Synthase: Structure01:18

ATP Synthase: Structure

ATP synthase or ATPase is among the most conserved proteins found in bacteria, mammals, and plants. This enzyme can catalyze a forward reaction in response to the electrochemical gradient, producing ATP from ADP and inorganic phosphate. ATP synthase can also work in a reverse direction by hydrolyzing ATP and generating an electrochemical gradient. Different forms of ATP synthases have evolved special features to meet the specific demands of the cell. Based on their specific feature, ATP...
15.4K
C4 Pathway and CAM01:27

C4 Pathway and CAM

Most plants use the C3 pathway for carbon fixation. However, some plants, such as sugar cane, corn, and cacti that grow in hot conditions, use alternative pathways to fix carbon and conserve energy loss due to photorespiration. Photorespiration is the process that occurs when the oxygen concentration is high. Under such conditions, the rubisco enzyme in the Calvin cycle binds O2 instead of CO2, which halts photosynthesis and consumes energy.
C4 Pathway
The C4 pathway is used by plants such as...
49.1K
Mechanisms of Retrovirus-induced Cancers01:51

Mechanisms of Retrovirus-induced Cancers

Retroviruses are RNA viruses that have been shown to cause cancers in diverse species, including chickens, mice, cats, and monkeys. The RNA genomes of these viruses are first reverse-transcribed into single and then double-stranded DNA (dsDNA) copies. This dsDNA called proviral DNA then integrates into the host genome. Subsequently, the host cell transcribes the proviral DNA in concert with the chromosomal DNA. This leads to the production of viral RNA and proteins that assemble at the host...
7.0K
Lung Capacity01:47

Lung Capacity

The air in the lungs is measured in volumes and capacities. Lung volume measures reflect the amount of air taken in, released, or left over after a lung function, like a single inhalation. Lung capacity measures are sums of two or more lung volume measures.
56.2K