Related Experiment Video

Updated: Mar 30, 2026

Through the Looking Glass: Time-lapse Microscopy and Longitudinal Tracking of Single Cells to Study Anti-cancer Therapeutics
06:00

Through the Looking Glass: Time-lapse Microscopy and Longitudinal Tracking of Single Cells to Study Anti-cancer Therapeutics

Published on: May 14, 2016

11.7K

The homeoprotein DLX3 and tumor suppressor p53 co-regulate cell cycle progression and squamous tumor growth

E Palazzo1, M Kellett1, C Cataisson2

  • 1Laboratory of Skin Biology, NIAMS, NIH, Bethesda, MD, USA.

Oncogene
|November 3, 2015
PubMed

Insights

The DLX3 protein network controls skin cell division and prevents skin cancer. Loss of DLX3 promotes tumor growth, while its restoration inhibits squamous cell carcinoma cell migration.

Area of Science:

  • Dermatology
  • Molecular Biology
  • Cancer Research

Background:

  • Epidermal homeostasis relies on regulated keratinocyte cell cycling.
  • Imbalances in cell cycle control can lead to neoplastic development.
  • The DLX3 protein's role in skin cancer is not well understood.

Purpose of the Study:

  • To investigate the function of a novel DLX3-dependent network in regulating epidermal hyperplasia and squamous tumorigenesis.
  • To elucidate the molecular mechanisms by which DLX3 influences the cell cycle and differentiation.
  • To determine the role of DLX3 in human skin cancers and squamous cell carcinoma (SCC) progression.

Main Methods:

  • Integrated genetic and transcriptomic approaches were used to identify DLX3-regulated pathways.
  • Physical interaction between DLX3 and p53 on the p21 promoter was assessed.
  • Keratinocyte cell cycle progression was analyzed following DLX3 manipulation.
  • ERK pathway activation was measured in DLX3-deficient cells.
  • DLX3 expression levels were examined in human skin cancers and experimentally induced mouse SCC.
  • The effect of DLX3 reinstatement on SCC cell migration and wound closure was evaluated.

Main Results:

  • A novel DLX3-dependent network was identified that constrains epidermal hyperplasia and squamous tumorigenesis.
  • DLX3 operates through a p53-regulated network, physically interacting with p53 on the p21 promoter to enhance p21 expression.
  • Elevated DLX3 in keratinocytes induced a G1-S cell cycle blockade with p53 transcriptional profiles.
  • DLX3 loss promoted a mitogenic phenotype with constitutive ERK activation.
  • DLX3 expression was lost in human skin cancers and decreased during SCC progression.
  • Restoring DLX3 function attenuated SCC cell migration and reduced wound closure.

Conclusions:

  • The DLX3-p53 interplay is a critical regulatory axis in epidermal differentiation and cell cycle control.
  • DLX3 acts as a tumor suppressor in the skin, inhibiting keratinocyte proliferation and SCC progression.
  • DLX3 loss is associated with skin carcinogenesis, highlighting its potential as a therapeutic target.

More Related Videos

Yeast As a Chassis for Developing Functional Assays to Study Human P5314:57

Yeast As a Chassis for Developing Functional Assays to Study Human P53

Published on: August 4, 2019

10.2K
Detection of Aggregation-Prone Behavior in Mutant P53 V157F Breast Cancer Cells Using Multipoint Thioflavin T Fluorescence04:56

Detection of Aggregation-Prone Behavior in Mutant P53 V157F Breast Cancer Cells Using Multipoint Thioflavin T Fluorescence

Published on: December 30, 2025

326

Related Concept Videos

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...
5.4K
Negative Regulator Molecules01:23

Negative Regulator Molecules

Positive regulators allow a cell to advance through cell cycle checkpoints. Negative regulators have an equally important role as they terminate a cell’s progression through the cell cycle—or pause it—until the cell meets specific criteria.
38.9K
DNA Damage can Stall the Cell Cycle02:36

DNA Damage can Stall the Cell Cycle

In response to DNA damage, cells can pause the cell cycle to assess and repair the breaks. However, the cell must check the DNA at certain critical stages during the cell cycle. If the cell cycle pauses before DNA replication, the cells will contain twice the amount of DNA. On the other hand, if cells arrest after DNA replication but before mitosis, they will contain four times the normal amount of DNA. With a host of specialized proteins at their disposal,cells must use the right protein at...
10.4K
DNA Damage Can Stall the Cell Cycle02:36

DNA Damage Can Stall the Cell Cycle

In response to DNA damage, cells can pause the cell cycle to assess and repair the breaks. However, the cell must check the DNA at certain critical stages during the cell cycle. If the cell cycle pauses before DNA replication, the cells will contain twice the amount of DNA. On the other hand, if cells arrest after DNA replication but before mitosis, they will contain four times the normal amount of DNA. With a host of specialized proteins at their disposal,cells must use the right protein at...
3.4K
Inhibition of Cdk Activity02:34

Inhibition of Cdk Activity

The orderly progression of the cell cycle depends on the activation of Cdk protein by binding to its cyclin partner. However, the cell cycle must be restricted when undergoing abnormal changes. Most cancers correlate to the deregulated cell cycle, and since Cdks are a central component of the cell cycle, Cdk inhibitors are extensively studied to develop anticancer agents. For instance, cyclin D associates with several Cdks, such as Cdk 4/6, to form an active complex. The cyclin D-Cdk4/6 complex...
6.2K
Molecular Factors Affecting Cell Division01:27

Molecular Factors Affecting Cell Division

Several external and internal factors influence the initiation and inhibition of cell division. For instance, the death of nearby cells or the release of human growth hormone (hGH) promotes cell division. In contrast, lack of hGH or crowding of cells can inhibit cell division.
Several proteins function as internal regulators to ensure each cell cycle stage is completed faithfully before proceeding to the next. Regulator molecules may act directly or influence the activity or production of other...
4.1K