Related Experiment Video
Updated: Apr 27, 2026
An Optimized Protocol for Electrophoretic Mobility Shift Assay Using Infrared Fluorescent Dye-labeled Oligonucleotides
Published on: November 29, 2016
Sox2 cooperates with Lkb1 loss in a mouse model of squamous cell lung cancer
Anandaroop Mukhopadhyay1, Kristofer C Berrett1, Ushma Kc1
1Department of Oncological Sciences, University of Utah and Huntsman Cancer Institute, Salt Lake City, UT 84112, USA.
Abstract:
Squamous cell carcinoma (SCC) of the lung is the second most common subtype of lung cancer. With limited treatment options, the 5-year survival rate of SCC is only 15%. Although genomic alterations in SCC have been characterized, identifying the alterations that drive SCC is critical for improving treatment strategies. Mouse models of SCC are currently limited. Using lentiviral delivery of Sox2 specifically to the mouse lung, we tested the ability of Sox2 to promote tumorigenesis in multiple tumor suppressor backgrounds. Expression of Sox2, frequently amplified in human SCC, specifically cooperates with loss of Lkb1 to promote squamous lung tumors. Mouse tumors exhibit characteristic histopathology and biomarker expression similar to human SCC. They also mimic human SCCs by activation of therapeutically relevant pathways including STAT and mTOR. This model may be utilized to test the contribution of additional driver alterations in SCC, as well as for preclinical drug discovery.
Insights
Sox2 cooperates with Lkb1 loss to drive squamous cell carcinoma (SCC) in mouse lungs. This new model mimics human lung SCC, aiding in the discovery of new treatments.
Area of Science:
- Oncology
- Genetics
- Molecular Biology
Background:
- Lung squamous cell carcinoma (SCC) is a major cancer subtype with poor prognosis.
- Limited effective treatments exist for lung SCC, necessitating research into its drivers.
- Current mouse models for lung SCC are insufficient for comprehensive study.
Purpose of the Study:
- To investigate the role of Sox2 in lung tumorigenesis.
- To develop a novel mouse model for studying lung SCC.
- To identify cooperating genetic alterations driving SCC development.
Main Methods:
- Lentiviral delivery of Sox2 to mouse lungs.
- Utilizing mouse models with deficiencies in tumor suppressor genes.
- Histopathological and molecular analysis of induced tumors.
Main Results:
- Sox2 expression, particularly with Lkb1 loss, induced squamous lung tumors in mice.
- The generated mouse tumors closely resemble human lung SCC in histology and biomarkers.
- Activated signaling pathways, including STAT and mTOR, were observed, mirroring human SCC.
Conclusions:
- Sox2 is a key driver of lung SCC, especially in the context of Lkb1 deficiency.
- The developed mouse model accurately recapitulates human lung SCC.
- This model is valuable for exploring additional SCC drivers and for preclinical drug discovery.
Related Concept Videos
01:33Pleiotropy
01:12Loss of Tumor Suppressor Gene Functions
When the tumor suppressor genes develop mutations or are lost, cells start growing out of control, leading to cancer. However, a single functional copy of the tumor suppressor gene is enough for the cells to maintain their normal functions and cell...
01:12Loss of Tumor Suppressor Gene Functions
01:05Cancer-Critical Genes II: Tumor Suppressor Genes
When the function of certain critical genes, especially those involved in cell cycle regulation and cell growth signaling cascades, gets disrupted, it upsets the cell cycle progression. Such cells with unchecked cell cycles start proliferating uncontrollably and eventually develop into tumors.
Such genes that act...
01:05Cancer-Critical Genes II: Tumor Suppressor Genes
01:20The Retinoblastoma Gene
The first-ever tumor suppressor gene called Rb was identified in retinoblastoma - a rare eye tumor in children. In inherited forms of the disease, a child inherits one defective copy of the Rb gene, which predisposes them to retinoblastoma. However,...