JoVE - Journal of Visualized Experiments
JoVE Visualize
Contact Us

The promotion of cell proliferation and invasion in cutaneous squamous cell carcinomas after ARNT downregulation is associated with CXCL3

  • 0Department of Dermatology, Ren Ji Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200127, China.
Cellular Signalling +

|

September 23, 2024

|

September 23, 2024

View abstract on PubMed

Summary

This summary is machine-generated.

The aryl hydrocarbon receptor nuclear translocator (ARNT) is downregulated in skin cancer, promoting tumor growth and metastasis. Targeting ARNT may offer a new therapeutic strategy for cutaneous squamous cell carcinoma (cSCC).

Area Of Science

  • Oncology
  • Molecular Biology
  • Cell Biology

Background

  • The aryl hydrocarbon receptor nuclear translocator (ARNT) is a transcription factor involved in cellular stress responses.
  • Its specific function in cutaneous squamous cell carcinoma (cSCC) pathogenesis is not well understood.

Purpose Of The Study

  • To investigate the role of ARNT in the development and progression of cSCC.
  • To explore ARNT's regulatory mechanisms in cSCC cells.

Main Methods

  • Immunohistochemistry was used to assess ARNT expression in cSCC tissues and cell lines.
  • ARNT was knocked down in A431 and SCL-1 cells to evaluate its impact on proliferation and metastasis.
  • Microarray analysis and Ingenuity Pathway Analysis were performed on ARNT-depleted cells.
  • Cellular and xenograft experiments were conducted to validate findings.

Main Results

  • ARNT expression was found to be downregulated in cSCC and precancerous lesions.
  • ARNT knockdown significantly increased cSCC cell growth and metastatic potential.
  • Loss of ARNT correlated with enhanced cell proliferation, movement, and upregulation of CXCL3.
  • ARNT regulates cSCC invasiveness via a CXCL3-dependent pathway, potentially involving ROS-STAT3 signaling.

Conclusions

  • ARNT plays a critical role in suppressing cSCC development by controlling proliferation and metastasis.
  • ARNT's regulation of CXCL3 expression is a key mechanism in its tumor-suppressive function.
  • ARNT represents a potential therapeutic target for cSCC treatment.

Keywords:

Related Concept Videos

Abnormal Proliferation 02:23

4.5K

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...

Role Of Notch Signalling In Intestinal Stem Cell Renewal 01:12

2.1K

Notch signaling was first discovered in Drosophila melanogaster, where it is involved in cell lineage differentiation. Notch signaling regulates the maintenance and differentiation of intestinal stem cells or ISCs by controlling the expression of atonal homolog 1 or Atoh1. Atoh1 directs cells to differentiate into secretory cells.
Direct cell-to-cell contact is needed for the activation of Notch signaling. The signal is initiated when a notch ligand binds to a receptor on an adjacent cell, also...

Receptor Downregulation in MVBs 01:15

2.0K

Multivesicular bodies (MVBs) are mature endosomes that sort ubiquitinated proteins and then fuse with lysosomes to degrade the sorted proteins. Epidermal growth factor (EGF) and its receptor (EGFR) form a complex that can be internalized through endocytosis, sorted into an MVB, and later degraded.
The EGFR can initiate signaling pathways that  lead to cell proliferation, migration, and differentiation. Overexpression of EGFR  stimulates cells to proliferate. Excessive  EGFR...

Mitogens and the Cell Cycle 02:38

6.4K

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...

Skin Cancer 01:30

4.0K

Skin cancer is a type of cancer that occurs when there is an abnormal growth of skin cells, usually triggered by damage to the DNA within the skin cells. It is primarily caused by exposure to ultraviolet (UV) radiation from the sun or artificial sources like tanning beds. Skin cancer is the most common type of cancer worldwide, and its incidence continues to rise.
Basal Cell Carcinoma (BCC): BCC is the most common type of skin cancer, accounting for about 80% of cases. It typically develops in...