JoVE - Journal of Visualized Experiments
JoVE Visualize
Contact Us

Pannexin 1 and pannexin 3 differentially regulate the cancer cell properties of cutaneous squamous cell carcinoma

  • 0Department of Anatomy and Cell Biology, Schulich School of Medicine and Dentistry, University of Western Ontario, London, Ontario, Canada.
The Journal of Physiology +

|

November 19, 2024

|

November 19, 2024

View abstract on PubMed

Summary

This summary is machine-generated.

Pannexin 1 (PANX1) promotes skin cancer growth and migration, while Pannexin 3 (PANX3) suppresses precancerous lesions. Their opposing roles in cutaneous squamous cell carcinoma (cSCC) offer potential therapeutic targets.

Area Of Science

  • Dermatology
  • Oncology
  • Molecular Biology

Background

  • Pannexin (PANX) channels are crucial for skin homeostasis and keratinocyte function.
  • Previous studies indicated reduced PANX1 and PANX3 in cutaneous squamous cell carcinoma (cSCC).

Purpose Of The Study

  • To investigate the expression and function of PANX1 and PANX3 in cSCC.
  • To determine the association between PANX1 and PANX3 dysregulation and cSCC malignancy.

Main Methods

  • Bioinformatic analysis of RNA-seq data from cSCC and normal tissues.
  • Analysis of patient-matched cSCC and skin samples for PANX1 and PANX3 expression.
  • CRISPR/Cas9 gene editing to delete PANX1 in SCC-13 cells.
  • Pharmacological inhibition of PANX1.
  • Utilizing a 7,12-dimethylbenz(a)anthracene/12-O-tetradecanoylphorbol-13-acetate (DMBA/TPA) mouse model with global Panx3 knockout (KO) mice.

Main Results

  • Bioinformatics revealed increased PANX1 transcripts in cSCC, but no difference in PANX3 mRNA.
  • Patient-matched samples showed decreased PANX3 transcripts and upregulated PANX1 protein in cSCC.
  • PANX1 upregulation correlated with larger tumor dimensions and promoted SCC cell growth and migration.
  • Panx3 KO mice exhibited increased incidence and volume of precancerous papillomas compared to wild-type mice.

Conclusions

  • PANX1 dysregulation promotes cSCC growth and malignancy.
  • PANX3 dysregulation is associated with increased susceptibility to and growth of precancerous lesions.
  • PANX1 and PANX3 exhibit opposing roles in keratinocyte transformation, with PANX1 being tumor-promoting and PANX3 being tumor-suppressive.

Keywords:

Related Concept Videos

Cancer Cell Migration through Invadopodia 01:35

2.3K

Invadosome is a broad category of cell surface structures with proteolytic activity that  degrades the extracellular matrix (ECM). Invadosomes are present in normal cell types, including macrophages, endothelial cells, and neurons, as well as tumor cells. Although the macrophage podosomes and tumor cell invadopodia are classified as invadosomes, they have different structures, molecular pathways, and functions. Podosomes are short structures that last for a few minutes. However,...

Interactions Between Signaling Pathways 01:19

6.2K

Signaling cascades usually lack linearity. Multiple pathways interact and regulate one another, allowing cells to integrate and respond to diverse environmental stimuli.
Convergence and divergence, and cross-talk between signaling pathways
Two distinct signaling pathways can converge on a single functional unit, which may either be a single protein or a complex of proteins. The response is either functionally distinct or synergistic between the two pathways but different from the response...

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...

Adaptive Mechanisms in Cancer Cells 02:53

5.7K

Cancer cells accumulate genetic changes at an abnormally rapid rate due to the defects in the DNA repair mechanisms. From an evolutionary perspective, such genetic instability is advantageous for cancer development. Mutant cell lines accumulate a series of beneficial mutations that contribute to their progression into cancer.
Some of the advantages that cancer cells have on normal cells include - enhanced ability to divide without terminally differentiating, induce new blood vessel formation,...

The Intrinsic Apoptotic Pathway 01:31

6.4K

Internal cellular stress, such as cellular injury or hypoxia, triggers intrinsic apoptosis. The B-cell lymphoma 2 (Bcl-2) family of proteins are the primary regulators of the intrinsic apoptotic pathway. For example, during DNA damage, checkpoint proteins, such as Ataxia Telangiectasia Mutated (ATM protein) and Checkpoints Factor-2 (Chk2) proteins, are activated. These proteins phosphorylate p53 which further activates pro-apoptotic proteins, such as Bax, Bak, PUMA, and Noxa, and inhibits...

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...