Related Experiment Video

Updated: Apr 25, 2026

The Soft Agar Colony Formation Assay
08:01

The Soft Agar Colony Formation Assay

Published on: October 27, 2014

112.5K

β-catenin contributes to lung tumor development induced by EGFR mutations

Sohei Nakayama1, Natasha Sng1, Julian Carretero2

  • 1Division of Hematology/Oncology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts.

Cancer Research
|August 29, 2014
PubMed

Insights

Beta-catenin is crucial for EGFR-mutated lung cancer development and resistance to EGFR tyrosine kinase inhibitors (TKIs). Targeting beta-catenin may offer new strategies for lung cancer treatment.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Genetics

Background:

  • Epidermal Growth Factor Receptor (EGFR) tyrosine kinase inhibitors (TKIs) have transformed lung cancer treatment.
  • Therapeutic resistance to EGFR TKIs is a significant clinical challenge, limiting long-term patient outcomes.
  • The underlying mechanisms of TKI resistance and lung tumorigenesis in EGFR-mutated cancers require further elucidation.

Purpose of the Study:

  • To investigate the role of beta-catenin in the development and progression of EGFR-mutated lung cancers.
  • To explore the potential of targeting the beta-catenin pathway as a therapeutic strategy for overcoming TKI resistance.

Main Methods:

  • Analysis of beta-catenin expression and activation in EGFR-mutated lung cancer cells.
  • Investigation of the interaction between mutant EGFR and beta-catenin, including tyrosine phosphorylation.
  • Assessment of beta-catenin's role in transactivation and its impact on TKI resistance.
  • Pharmacological inhibition and genetic deletion of beta-catenin in preclinical lung cancer models.

Main Results:

  • Beta-catenin was found to be upregulated and activated in EGFR-mutated lung cancer cells.
  • Mutant EGFR directly interacted with and tyrosine phosphorylated beta-catenin, enhancing its activity.
  • This interaction was particularly pronounced in cells with the T790M resistance mutation.
  • Inhibition or deletion of beta-catenin significantly suppressed tumor growth and formation in EGFR-mutated lung cancer models, including those resistant to TKIs.

Conclusions:

  • Beta-catenin is a key mediator in EGFR-mutated lung tumorigenesis.
  • The beta-catenin pathway is essential for the development of resistance to EGFR TKIs.
  • Targeting beta-catenin represents a promising therapeutic avenue for treating EGFR-mutated lung cancer and overcoming TKI resistance.

More Related Videos

An Immunofluorescent Method for Characterization of Barrett’s Esophagus Cells08:54

An Immunofluorescent Method for Characterization of Barrett’s Esophagus Cells

Published on: July 20, 2014

13.1K
Reconstitution Of β-catenin Degradation In Xenopus Egg Extract09:41

Reconstitution Of β-catenin Degradation In Xenopus Egg Extract

Published on: June 17, 2014

10.9K

Related Concept Videos

Catenins01:23

Catenins

Catenins are characterized by multiple binding domains and dynamic structures that allow them to function as linker proteins in cell junction complexes. All catenins, except α-catenin, contain a characteristic protein sequence called the armadillo repeat and are therefore also called armadillo proteins.
Catenins in Cell Junctions
Catenins bind to cell adhesion molecules such as cadherins and link them to different cytoskeletal proteins depending on the type of cell junction. At the...
2.2K
Cadherins in Tissue Organization01:19

Cadherins in Tissue Organization

The cadherins are a superfamily of cell adhesion molecules comprising over 180 variants, with specific tissues expressing a particular combination of cadherin types. Cadherins generally exhibit homophilic binding; i.e., cadherins on one cell bind to cadherins of the same or closely related type on another cell. Thus, cells of the same type have a specific affinity to bind to each other and sort themselves into clusters to form tissues.
Cell Sorting During Development
Cell sorting plays an...
3.5K
Canonical Wnt Signaling Pathway02:54

Canonical Wnt Signaling Pathway

The gene encoding the main signaling molecules of the Wnt signaling pathways (the Wnt proteins) was discovered almost four decades ago by Nüsslein-Volhard and Wieschaus. They identified and originally named the gene "wingless" (wg) after a phenotype discovered during their landmark genetic screen in Drosophila for body pattern defects. At around the same time, another researcher named Harold Varmus found that a murine tumor virus activates the mammalian wg homolog, Int-1, which...
8.6K
Mitogens and the Cell Cycle02:38

Mitogens and the Cell Cycle

Mitogens and their receptors play a crucial role in controlling the progression of the cell cycle. However, the loss of mitogenic control over cell division leads to tumor formation. Therefore, mitogens and mitogen receptors play an important role in cancer research. For instance, the epidermal growth factor (EGF) - a type of mitogen and its transmembrane receptor (EGFR), decides the fate of the cell's proliferation. When EGF binds to EGFR, a member of the ErbB family of tyrosine kinase...
6.3K
Tumor Progression02:07

Tumor Progression

Tumor progression is a phenomenon where the pre-formed tumor acquires successive mutations to become clinically more aggressive and malignant. In the 1950s, Foulds first described the stepwise progression of cancer cells through successive stages.
Colon cancer is one of the best-documented examples of tumor progression. Early mutation in the APC gene in colon cells causes a small growth on the colon wall called a polyp. With time, this polyp grows into a benign, pre-cancerous tumor. Further...
6.2K
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...
3.6K