Polysialylated NCAM represses E-cadherin-mediated cell-cell adhesion in pancreatic tumor cells

Susanne C Schreiber1, Klaudia Giehl, Caroline Kastilan

  • 1Institute of Zoology 2, University Karlsruhe, Karlsruhe, Germany.

Gastroenterology
|April 4, 2008
PubMed
Abstract

Insights

Oncogenic K-Ras induces polysialylated neural cell adhesion molecule (PSA-NCAM), which disrupts E-cadherin adhesion. This promotes pancreatic tumor cell migration and metastasis.

Area of Science:

  • Cell Biology
  • Cancer Research
  • Molecular Oncology

Background:

  • Tumor metastasis involves reduced epithelial cell-cell adhesion.
  • E-cadherin-mediated adherens junctions are crucial for cell adhesion.
  • Perturbation of E-cadherin is essential for tumor cell dissemination.

Purpose of the Study:

  • To investigate the interaction between PSA-NCAM and E-cadherin.
  • To determine the role of PSA-NCAM in pancreatic tumor cell invasion.
  • To elucidate the mechanism by which K-Ras influences cell adhesion.

Main Methods:

  • Coimmunoprecipitation assays to study protein interactions.
  • Cell-cell aggregation and migration assays to assess invasion.
  • Enzymatic removal of PSA and siRNA to down-regulate PSA-transferases.

Main Results:

  • Oncogenic K-Ras induced PSA-NCAM expression in pancreatic cells, reducing E-cadherin adhesion.
  • PSA-NCAM association with E-cadherin correlated with decreased aggregation and increased migration.
  • PSA removal or reduced PSA-transferase expression restored cell adhesion and reduced migration.

Conclusions:

  • Oncogenic K-Ras induces PSA-NCAM, a novel mechanism reducing E-cadherin adhesion.
  • This process facilitates pancreatic tumor cell dissemination.
  • Targeting PSA-NCAM may offer therapeutic strategies for metastasis.

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...
Immunoglobulin-like Cell Adhesion Molecules01:31

Immunoglobulin-like Cell Adhesion Molecules

Immunoglobulin-like cell adhesion molecules or Ig-CAMs are a versatile group of cell surface glycoproteins belonging to the immunoglobulin protein superfamily. Ig-CAMs possess the characteristic immunoglobulin protein domains and other domains such as the fibronectin type III domain. The Ig domains are glycosylated to varying degrees in different Ig-CAMs.
Ig-CAMs exhibit either homophilic binding (to other Ig-CAMs) or heterophilic binding (to other ligands such as integrins). While most Ig-CAMs...
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 diversity of cadherins...
Cell Adhesion Molecules - Types and Functions01:20

Cell Adhesion Molecules - Types and Functions

Cell adhesion molecules (CAMs) are pivotal to multicellularity and the coordinated functioning of tissues and organ systems. They enable physical interactions between cells and provide mechanical strength to tissues. They also function as receptors for signal transmission across the plasma membrane. The CAMs are broadly classified into four families - integrins, cadherins, selectins, and immunoglobulin-like CAMs (IgCAMs).
CAM Families
The Integrin family of proteins is primarily  involved in a...
Selectins01:25

Selectins

Cell adhesion is  an essential aspect of multicellularity. While stable cell interactions usually occur between cells of the same type, transient cell interactions occur between cells of different tissue types, such as between neutrophils and endothelial cells. Selectins are one class of cell adhesion molecules (CAMs) that bind carbohydrate ligands to form transient cell adhesion. They are rod-like proteins with a long extracellular part of variable length ending with the lectin domain, which...
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 adherens...