FYNagling divergent adhesive functions for Fyn in keratinocytes

Sarah E Fenton1, Mitchell F Denning

  • 1Molecular Biology Program, Cardinal Bernardin Cancer Center, Loyola University Chicago, Maywood, IL, USA.

Insights

Fyn kinase has dual roles in keratinocyte (KC) adhesion, promoting it during differentiation but hindering it in cancer. This review proposes hypotheses to unify Fyn's contradictory functions in cell adhesion.

Area of Science:

  • Cell Biology
  • Biochemistry
  • Dermatology

Background:

  • Fyn, a Src family kinase (SFK), exhibits paradoxical roles in keratinocyte (KC) adhesion.
  • Physiological Fyn activation supports KC differentiation and adherens junction formation.
  • Aberrant Fyn activity in cancer is linked to adhesion loss and increased migration.

Purpose of the Study:

  • To reconcile conflicting literature on Fyn's function in KC cell-cell and cell-matrix adhesion.
  • To propose unifying hypotheses for Fyn's diverse roles in keratinocyte adhesion dynamics.
  • To provide testable hypotheses for future research into Fyn's regulatory mechanisms.

Main Methods:

  • Literature review and synthesis of existing research on Fyn kinase.
  • Analysis of Fyn's involvement in various adhesion structures (adherens junctions, focal adhesions, desmosomes, hemidesmosomes).
  • Development of theoretical frameworks to explain Fyn's context-dependent functions.

Main Results:

  • Fyn's activity is context-dependent, influencing different adhesion types.
  • Fyn can both promote and inhibit adhesion complex formation and stability.
  • Fyn's role varies significantly between normal differentiation and oncogenic transformation.

Conclusions:

  • Fyn's seemingly contradictory roles in keratinocyte adhesion can be explained by context-specific mechanisms.
  • Further research is needed to elucidate the precise molecular pathways mediating Fyn's dual functions.
  • Understanding Fyn's regulation is crucial for targeting keratinocyte-related diseases and cancer progression.

Related Concept Videos

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...
2.7K
Anchoring Junctions01:03

Anchoring Junctions

Anchoring junctions are multiprotein complexes that help cells connect to other cells and the extracellular matrix. Anchoring junctions are present on the lateral and basal surfaces of cells, providing strong and flexible connections. Focal adhesions are often formed due to cell interactions with the ECM substrata, which initiate signal transduction via kinase cascades and other mechanisms. Together, they provide stability and tissue integrity. There are three types of anchoring junctions:...
4.2K
Fibronectins Connect Cells with ECM01:25

Fibronectins Connect Cells with ECM

Fibronectin is an adhesive glycoprotein present in the extracellular matrix of embryogenic and adult tissue. These molecules primarily aid in regulating cell motility and attachment. A fibronectin molecule is composed of two identical polypeptide chains attached to each other by a pair of disulfide bonds at the C-terminal.
Both proteoglycans and collagen are attached to fibronectin proteins, which, in turn, are attached to integrin proteins. These integrin proteins interact with transmembrane...
2.9K
Role of Ephrin-Eph Signalling in Intestinal Stem Cell Renewal01:22

Role of Ephrin-Eph Signalling in Intestinal Stem Cell Renewal

Erythropoietin-producing hepatocellular carcinoma receptor (Eph) and its ligand, Eph receptor-interacting protein (Ephrin) were first discovered in the human carcinoma cell line, hence the name. Ephrin-Eph interaction guides cells to reach their appropriate location in adult tissues. They also play an essential role in the immune system by helping in immune cell migration, adhesion, and activation. Based on their structure and function, Eph is divided into two classes — EphA and EphB.
1.8K
Introduction to Fibroblasts01:09

Introduction to Fibroblasts

Rudolph Virchow discovered spindle-shaped cells called fibroblasts in 1858. Inactive fibroblasts, called fibrocytes, become activated by various stimuli, such as growth factors and inflammatory cytokines. Activated fibroblasts play a crucial role in wound healing, inflammation, formation of new blood vessels, and cancer progression. Uncontrolled activation of fibroblasts results in fibrosis, the excess deposition of fibrous tissue, which can lead to scarring and affect normal organs. This...
3.9K
Tension Response at Adherens Junctions01:26

Tension Response at Adherens Junctions

The adherens junctions that anchor cells together are multi-protein complexes that dynamically adapt to mechanical stimuli such as tensile forces and shear stress. Mechanosensory proteins in these junctions can sense such mechanical stimuli and undergo a shift in their conformation, resulting in an altered function — a process called mechanotransduction.
α-Catenin as a Mechanosensory Protein
The α-catenin of adherens junctions is an allosteric protein with three VH (vinculin...
3.2K