Related Experiment Video

Updated: Nov 6, 2025

Multidimensional Coculture System to Model Lung Squamous Carcinoma Progression
07:53

Multidimensional Coculture System to Model Lung Squamous Carcinoma Progression

Published on: March 17, 2020

7.4K

Loss of DLX3 tumor suppressive function promotes progression of SCC through EGFR-ERBB2 pathway

Deepti Bajpai1, Spencer Mehdizadeh1, Akihiko Uchiyama2

  • 1Laboratory of Skin Biology, National Institute of Arthritis and Musculoskeletal and Skin Diseases, NIH, Bethesda, MD, USA.

Oncogene
|May 5, 2021
PubMed

Insights

DLX3 acts as a tumor suppressor in cutaneous squamous cell carcinoma (cSCC). Loss of DLX3 accelerates skin tumor development and activates the EGFR-ERBB2 pathway, suggesting new therapeutic targets.

Area of Science:

  • Oncology
  • Dermatology
  • Molecular Biology

Background:

  • Cutaneous squamous cell carcinoma (cSCC) is the second most common skin cancer.
  • Disrupted keratinocyte proliferation and differentiation underlie cSCC development.
  • DLX3, a homeobox transcription factor, is crucial for epidermal homeostasis.

Purpose of the Study:

  • To investigate the role of DLX3 expression in cSCC prognosis.
  • To model the function of Dlx3 in skin tumorigenesis.
  • To identify molecular pathways affected by Dlx3 loss in cSCC.

Main Methods:

  • Clinicopathologic analysis of DLX3 expression in human cSCC.
  • Kaplan-Meier survival analysis.
  • A two-stage DMBA/TPA skin tumorigenesis study in Dlx3 conditional knockout (Dlx3cKO) mice.
  • Whole transcriptome analysis of mouse tumor and skin tissue.

Main Results:

  • Higher DLX3 protein expression correlated with lower cSCC pathologic grade.
  • Low DLX3 expression was associated with poor patient survival.
  • Dlx3cKO mice exhibited increased tumor incidence and accelerated tumorigenesis.
  • Loss of Dlx3 led to spontaneous activation of the EGFR-ERBB2 pathway.

Conclusions:

  • DLX3 functions as a tumor suppressor in the skin.
  • Therapeutic strategies targeting the EGFR-ERBB2 pathway may be effective for cSCC.

More Related Videos

Modeling Oral-Esophageal Squamous Cell Carcinoma in 3D Organoids10:43

Modeling Oral-Esophageal Squamous Cell Carcinoma in 3D Organoids

Published on: December 23, 2022

3.7K
Establishment and Analysis of Tumor Slice Explants As a Prerequisite for Diagnostic Testing11:00

Establishment and Analysis of Tumor Slice Explants As a Prerequisite for Diagnostic Testing

Published on: November 29, 2018

14.6K

Related Concept Videos

Loss of Tumor Suppressor Gene Functions01:12

Loss of Tumor Suppressor Gene Functions

Tumor suppressor genes are normal genes that can slow down cell division, repair DNA mistakes, or program the cells for apoptosis in case of irreparable damage. Hence, they play an essential role in preventing the proliferation of damaged cells.
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...
5.4K
Abnormal Proliferation02:23

Abnormal Proliferation

Under normal conditions, most adult cells remain in a non-proliferative state unless stimulated by internal or external factors to replace lost cells. Abnormal cell proliferation is a condition in which the cell's growth exceeds and is uncoordinated with normal cells. In such situations, cell division persists in the same excessive manner even after cessation of the stimuli, leading to persistent tumors. The tumor arises from the damaged cells that replicate to pass the damage to the...
4.8K
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...
6.8K
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...
7.2K
The Retinoblastoma Gene01:20

The Retinoblastoma Gene

Tumor suppressor genes are normal genes that can slow down cell division, repair DNA mistakes, or program the cells for apoptosis in case of irreparable damage. Hence, they play an essential role in preventing the proliferation of damaged cells.
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,...
4.3K
Cancer-Critical Genes II: Tumor Suppressor Genes01:05

Cancer-Critical Genes II: Tumor Suppressor Genes

Genes usually encode proteins necessary for the proper functioning of a healthy cell. Mutations can often cause changes to the gene expression pattern, thereby altering the phenotype.
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...
8.5K