Related Experiment Video

Updated: Jan 31, 2026

Establishing Dual Resistance to EGFR-TKI and MET-TKI in Lung Adenocarcinoma Cells In Vitro with a 2-step Dose-escalation Procedure
09:38

Establishing Dual Resistance to EGFR-TKI and MET-TKI in Lung Adenocarcinoma Cells In Vitro with a 2-step Dose-escalation Procedure

Published on: August 11, 2017

9.2K

Semaphorin 7A promotes EGFR-TKI resistance in EGFR mutant lung adenocarcinoma cells

Yuhei Kinehara1,2,3, Izumi Nagatomo2, Shohei Koyama1,2,3

  • 1Department of Immunopathology, World Premier International Research Center, Immunology Frontier Research Center, Osaka University, Suita, Osaka, Japan.

JCI Insight
|December 21, 2018
PubMed

Insights

Semaphorin 7A (SEMA7A) drives resistance to EGFR tyrosine kinase inhibitors (EGFR-TKIs) in lung cancer by inhibiting apoptosis via ERK activation. SEMA7A may serve as a predictive biomarker and therapeutic target for EGFR-mutant lung adenocarcinoma.

Area of Science:

  • Oncology
  • Molecular Biology
  • Biochemistry

Background:

  • EGFR tyrosine kinase inhibitors (EGFR-TKIs) show initial efficacy in EGFR-mutant lung adenocarcinoma but are often limited by resistance.
  • A significant portion of patients (30-40%) exhibit poor response or relapse due to acquired resistance.
  • Identifying mechanisms of resistance and novel therapeutic targets is crucial for improving patient outcomes.

Purpose of the Study:

  • To investigate the role of semaphorin 7A (SEMA7A) in EGFR-TKI resistance in EGFR-mutant lung adenocarcinoma.
  • To elucidate the signaling pathways involved in SEMA7A-mediated resistance.
  • To evaluate SEMA7A as a potential predictive biomarker and therapeutic target.

Main Methods:

  • Analysis of SEMA7A expression in human lung adenocarcinoma specimens and correlation with mTOR activation.
  • Cell culture and animal models to assess the impact of SEMA7A modulation on EGFR-TKI sensitivity.
  • Investigation of the underlying molecular mechanisms, including apoptosis and ERK signaling pathways.
  • Assessment of integrin β1 (ITGB1) involvement in SEMA7A-mediated resistance.
  • Correlation of SEMA7A expression with clinical response to EGFR-TKI treatment.

Main Results:

  • SEMA7A is highly induced by the EGFR pathway via mTOR signaling and its expression correlates with mTOR activation in lung adenocarcinoma.
  • Loss of SEMA7A decreased EGFR-TKI resistance, while its overexpression increased resistance.
  • SEMA7A-mediated resistance is associated with inhibited apoptosis due to aberrant ERK activation.
  • Knockdown of integrin β1 (ITGB1) suppressed the ERK signaling pathway.
  • Higher SEMA7A expression in clinical samples predicted poorer response to EGFR-TKI treatment.

Conclusions:

  • The SEMA7A-ITGB1 axis plays a critical role in EGFR-TKI resistance in EGFR-mutant lung adenocarcinoma by activating ERK and inhibiting apoptosis.
  • SEMA7A is a potential predictive biomarker for EGFR-TKI treatment response.
  • SEMA7A represents a promising novel therapeutic target for overcoming EGFR-TKI resistance.
Keywords:
Drug therapyLung cancerOncologyPulmonology

More Related Videos

Profiling Sensitivity to Targeted Therapies in EGFR-Mutant NSCLC Patient-Derived Organoids08:52

Profiling Sensitivity to Targeted Therapies in EGFR-Mutant NSCLC Patient-Derived Organoids

Published on: November 22, 2021

4.6K
Identification of EGFR and RAS Inhibitors using Caenorhabditis elegans08:12

Identification of EGFR and RAS Inhibitors using Caenorhabditis elegans

Published on: October 5, 2020

3.4K

Related Concept Videos

The Eukaryotic Promoter Region02:40

The Eukaryotic Promoter Region

The eukaryotic promoter region is a segment of DNA located upstream of a gene. It contains an RNA polymerase binding site, a transcription start site, and several cis-regulatory sequences.  The proximal promoter region is located in the vicinity of the gene and has cis-regulatory sequences and the core promoter. The core promoter is the binding site for RNA polymerase and is usually located between -35 and +35 nucleotides from the transcription start site. The distal promoter regions are...
18.8K
The Eukaryotic Promoter Region02:40

The Eukaryotic Promoter Region

3.9K
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.
56.3K
Resistivity01:22

Resistivity

When a voltage is applied to a conductor, an electrical field is generated, and charges in the conductor feel the force due to the electrical field. The current density that results depends on the electrical field and the properties of the material. In some materials, including metals at a given temperature, the current density is approximately proportional to the electrical field. In these cases, the current density can be modeled as:
4.6K
Resistance01:19

Resistance

When a current moves through any conductor, the conductor causes some level of difficulty for the current to flow. The measure of that difficulty is known as the resistance of the material and is represented by R. Every material has its own resistance. In the case of conductors, heat is emitted whenever a current passes through them. Resistance depends on the resistivity of the material. Resistivity is a characteristic of the material used to fabricate electrical components, whereas the...
6.0K
Anaphase Promoting Complex00:50

Anaphase Promoting Complex

The stepwise destruction of specific proteins is necessary for the progression and completion of the cell cycle. Such proteins are ubiquitinated by ubiquitin ligases and then subsequently destroyed by the proteasome. The SCF (Skp1/Cullin/F-box) and the anaphase-promoting complex (APC) are two important ubiquitin ligases involved in cell cycle progression. While SCF is active throughout the cell cycle, APC gets activated during metaphase to anaphase transition. Cdc20 or Cdh1 binds to APC and...
3.4K