Related Experiment Video

Updated: Jun 10, 2026

Spatial and Temporal Control of Murine Melanoma Initiation from Mutant Melanocyte Stem Cells
06:09

Spatial and Temporal Control of Murine Melanoma Initiation from Mutant Melanocyte Stem Cells

Published on: June 7, 2019

Pro-prion binds filamin A, facilitating its interaction with integrin beta1, and contributes to melanomagenesis

Chaoyang Li1, Shuiliang Yu, Fumihiko Nakamura

  • 1Department of Pathology, School of Medicine, Case Western Reserve University, Cleveland, Ohio 44106, USA.

The Journal of Biological Chemistry
|July 24, 2010
PubMed

Insights

Filamin A (FLNA) integrates cell mechanics and signaling. The prion protein

Area of Science:

  • Cell Biology
  • Biochemistry
  • Oncology

Background:

  • Filamin A (FLNA) is crucial for cell mechanics and signaling, with its sufficiency linked to melanoma cell spreading and migration.
  • Normal prion protein (PrP) in melanoma cells retains its GPI anchor peptide signal sequence (GPI-PSS), which binds FLNA.
  • Integrin β1 also interacts with FLNA, forming distinct complexes.

Purpose of the Study:

  • To investigate the role of pro-PrP in FLNA-mediated cell spreading and migration.
  • To elucidate the interaction between pro-PrP, FLNA, and integrin β1 in melanoma cells.
  • To determine the contribution of pro-PrP to melanomagenesis.

Main Methods:

  • Comparing FLNA-sufficient (A7) and FLNA-deficient (M2) melanoma cells.
  • Analyzing the effect of reducing PrP expression on FLNA distribution and cell migration.
  • Investigating the formation of FLNA-PrP and FLNA-integrin β1 complexes.
  • Utilizing a synthetic PrP GPI-PSS peptide to inhibit cell spreading and migration.

Main Results:

  • Reducing PrP expression in A7 cells disrupted FLNA organization, actin organization, cell spreading, and migration.
  • FLNA forms two independent complexes: FLNA-PrP and FLNA-integrin β1.
  • Decreased PrP expression reduced integrin β1 binding to FLNA.
  • A synthetic PrP GPI-PSS peptide inhibited A7 cell spreading and migration.

Conclusions:

  • FLNA does not act alone; pro-PrP binding enhances FLNA-integrin β1 association, promoting melanoma cell spreading and migration.
  • Pro-PrP is present in melanoma in situ and is elevated in invasive melanoma.
  • The pro-PrP-FLNA interaction contributes to melanomagenesis.

More Related Videos

Screening for Melanoma Modifiers using a Zebrafish Autochthonous Tumor Model10:23

Screening for Melanoma Modifiers using a Zebrafish Autochthonous Tumor Model

Published on: November 13, 2012

Related Concept Videos

Mechanism of Filopodia Formation01:39

Mechanism of Filopodia Formation

Filopodia are thin, actin-rich cellular protrusions that play an important role in many fundamental cellular functions. They vary in their occurrence, length, and positioning in different cell types, suggesting their diverse roles.
Their main function is to guide migrating cells during normal tissue morphogenesis or cancer metastasis by recognizing and making initial contacts with the extracellular matrix. However, they can also act as stationary cell anchors or help to establish communication...
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...
Cytoskeletal Linker Proteins - Plakins01:09

Cytoskeletal Linker Proteins - Plakins

Plakins are large proteins with binding domains for microtubules, microfilaments, intermediate filaments, and membrane-associated protein complexes at cell junctions. Plakin functions are evolutionarily conserved and are primarily involved in organizing the different components of the cytoskeleton by crosslinking them to each other and connecting them to the cell-matrix and cell adhesion complexes. They are also known to interact with signal transducers, serve as scaffolds for signaling...
Integrins01:10

Integrins

Animal and protozoan cells do not have cell walls to help maintain shape and provide structural stability. Instead, these eukaryotic cells secrete a sticky mass of carbohydrates and proteins into the spaces between adjacent cells. This network of proteins and molecules is called an extracellular matrix or ECM.
Some ECM proteins assemble into a basement membrane to which the remaining components adhere. Proteoglycans typically form the bulk of the ECM while fibrous proteins, like collagen,...
Cytoskeletal Accessory Proteins01:13

Cytoskeletal Accessory Proteins

The cytoskeleton is an essential cell component that plays several structural and functional roles. However, the filaments that make up the cytoskeleton cannot function independently and depend on the accessory or ancillary proteins to effectively carry out their function. Accessory proteins associate with cytoskeletal filaments and their monomers, aiding filament formation and function. They also help in the cross-communication among cytoskeletal filaments. Cytoskeletal accessory proteins are...
Activation of Integrins01:15

Activation of Integrins

Integrins bind ligands and transmit information from outside the cell to inside or vice-versa through an "outside-in signaling" or "inside-out signaling."
In "outside-in signaling," external factors in the extracellular space bind to exposed ligand binding sites on integrins. This causes the inactive protein to undergo a conformational change to become active. Integrins are often clustered on the cell membrane. Repetitive and regularly spaced ligand binding events provide an effective stimulus.