Impact of Small Molecules on β-Catenin and E-Cadherin Expression in HPV16-positive and -negative Squamous Cell

Benedikt Kramer1, Clemens Hock2, Johannes David Schultz3

  • 1Department of Otorhinolaryngology Head and Neck Surgery, University Hospital Mannheim, Medical Faculty Mannheim, University Heidelberg, Mannheim, Germany benedikt.kramer@umm.de.

Anticancer Research
|May 29, 2017
PubMed
Abstract

Insights

Tyrosine kinase inhibitors impact β-catenin and E-cadherin expression in head and neck squamous cell carcinoma (SCC). These findings offer insights for developing targeted therapies for SCC, regardless of human papillomavirus (HPV) status.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Research

Background:

  • Head and neck squamous cell carcinoma (SCC) requires validation of molecular targets.
  • β-Catenin and E-cadherin are key in cancer progression via epithelial-mesenchymal transition.
  • Human papillomavirus (HPV) status influences SCC characteristics.

Purpose of the Study:

  • To investigate the effect of tyrosine kinase inhibitors (nilotinib, dasatinib, erlotinib, gefitinib) on β-catenin and E-cadherin expression in SCC.
  • To analyze these effects in relation to HPV status.

Main Methods:

  • Enzyme-linked immunosorbent assay (ELISA) was used to analyze protein expression.
  • SCC cell lines (UMSCC 11A, UMSCC 14C, CERV196) were treated with tyrosine kinase inhibitors.
  • Experiments were conducted in vitro.

Main Results:

  • All tested agents reduced β-catenin and E-cadherin expression in HPV16-negative SCC cells.
  • Gefitinib and dasatinib increased E-cadherin expression in HPV16-positive SCC cells.
  • Significant impacts on β-catenin and E-cadherin were observed in both HPV16-positive and HPV16-negative cells.

Conclusions:

  • Tyrosine kinase inhibitors significantly alter β-catenin and E-cadherin expression in head and neck SCC cells in vitro.
  • These molecular alterations may offer novel insights for targeted SCC therapies.
  • The study highlights the potential of targeting these proteins for therapeutic strategies in head and neck SCC.

Related Concept Videos

Cadherins in Tissue Organization01:19

Cadherins in Tissue Organization

The cadherins are a superfamily of cell adhesion molecules comprising over 180 variants, with specific tissues expressing a particular combination of cadherin types. Cadherins generally exhibit homophilic binding; i.e., cadherins on one cell bind to cadherins of the same or closely related type on another cell. Thus, cells of the same type have a specific affinity to bind to each other and sort themselves into clusters to form tissues.
Cell Sorting During Development
Cell sorting plays an...
4.4K
Catenins01:23

Catenins

Catenins are characterized by multiple binding domains and dynamic structures that allow them to function as linker proteins in cell junction complexes. All catenins, except α-catenin, contain a characteristic protein sequence called the armadillo repeat and are therefore also called armadillo proteins.
Catenins in Cell Junctions
Catenins bind to cell adhesion molecules such as cadherins and link them to different cytoskeletal proteins depending on the type of cell junction. At the...
3.2K
Structure of Cadherins01:25

Structure of Cadherins

The cadherins were one of the first cell adhesion molecules discovered; the term “cadherins”   is based on their calcium-dependent adhering properties. The first cadherins discovered on the epithelial, neuronal, and placental cells were named E-cadherin, P-cadherin, and N-cadherin, respectively. These classical cadherins share sequence and structural similarities. Other cadherins, including those involved in cell signaling, are grouped into non-classical cadherins. This...
5.0K
Intracellular Signaling Affects Focal Adhesions01:17

Intracellular Signaling Affects Focal Adhesions

Integrins act both as extracellular input receivers and as intracellular processing activators. As their name suggests, integrins are entirely integrated into the membrane structure. Their hydrophobic membrane-spanning regions interact with the phospholipid bilayer's hydrophobic region. These membrane receptors provide extracellular attachment sites for effectors like hormones and growth factors. They activate intracellular response cascades when their effectors are bound and active.
Some...
3.7K
Canonical Wnt Signaling Pathway02:54

Canonical Wnt Signaling Pathway

The gene encoding the main signaling molecules of the Wnt signaling pathways (the Wnt proteins) was discovered almost four decades ago by Nüsslein-Volhard and Wieschaus. They identified and originally named the gene "wingless" (wg) after a phenotype discovered during their landmark genetic screen in Drosophila for body pattern defects. At around the same time, another researcher named Harold Varmus found that a murine tumor virus activates the mammalian wg homolog, Int-1, which...
10.8K
Metastasis02:30

Metastasis

Metastasis is the spread of cancer cells from the original site to distant locations in the body. Cancer cells can spread via blood vessels (hematogenous) as well as lymph vessels in the body.
Epithelial-to-Mesenchymal Transition
The epithelial-to-mesenchymal transition or EMT is a developmental process commonly observed in wound healing, embryogenesis, and cancer metastasis. EMT is induced by transforming growth factor-beta (TGF-β) or receptor tyrosine kinase (RTK) ligands, which further...
6.7K