AIM1 is an actin-binding protein that suppresses cell migration and micrometastatic dissemination

Michael C Haffner1,2, David M Esopi1, Alcides Chaux2,3

  • 1Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore, MD, USA.

Nature Communications
|July 28, 2017
PubMed

Insights

Absent in melanoma 1 (AIM1) suppresses cancer cell invasion by regulating the actin cytoskeleton. Loss of AIM1 promotes prostate cancer cell migration, invasion, and metastasis, indicating its role as a tumor suppressor.

Area of Science:

  • Molecular Biology
  • Cancer Research
  • Cell Biology

Background:

  • Cancer cell migration and invasion are hallmarks of primary and metastatic cancers.
  • Altered cytoskeletal dynamics, particularly involving β-actin, are crucial for these invasive properties.

Purpose of the Study:

  • To identify novel actin-binding proteins that regulate cancer cell invasion.
  • To investigate the role of Absent in melanoma 1 (AIM1) in prostate cancer progression.

Main Methods:

  • Depletion of AIM1 in prostate epithelial cells.
  • Assessment of cytoskeletal remodeling, cell migration, invasion, and anchorage-independent growth.
  • In vivo studies to evaluate metastatic dissemination.
  • Analysis of AIM1 expression and localization in normal and cancerous prostate tissues.

Main Results:

  • AIM1 depletion increased cytoskeletal remodeling, intracellular traction forces, cell migration, invasion, and anchorage-independent growth.
  • Reduced AIM1 expression led to increased metastatic dissemination in vivo.
  • AIM1 associated with the actin cytoskeleton in normal prostate cells but was mislocalized in prostate cancers.
  • Advanced prostate cancers showed AIM1 deletion and reduced expression.

Conclusions:

  • AIM1 acts as a suppressor of pro-invasive phenotypes in prostate epithelial cells.
  • Dysregulation of AIM1, including mislocalization and reduced expression, is implicated in primary and metastatic prostate cancer.
  • AIM1 is a potential therapeutic target for suppressing prostate cancer invasion and metastasis.

Related Concept Videos

Role of Myosin in Cell Migration01:18

Role of Myosin in Cell Migration

Myosins are multimeric motor proteins involved in various cellular processes such as migration, adhesion, and proliferation. Myosin II is the most common type in animal cells, which binds and cross-links actin filaments.
Myosin II  is a hexamer comprising two heavy chains with globular heads and coiled-coil tails, two regulatory light chains, and two essential light chains. The ATPase sites on the myosin heads hydrolyze ATP, and the released phosphate generates the force for contraction....
3.5K
Cancer Cell Migration through Invadopodia01:35

Cancer Cell Migration through Invadopodia

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,...
3.4K
Actin Polymerization and Cell Motility01:13

Actin Polymerization and Cell Motility

Actin is a family of globular proteins that are highly abundant in eukaryotic cells. It makes up approximately 1-5% of total cell protein concentration. Actin monomers polymerize to form a complex network of polarized filaments, the actin cytoskeleton, that plays a crucial role in many cellular processes, including cell motility, division, endocytosis, and metastasis of cancer cells.
Actin cytoskeleton dynamics can produce pushing, pulling, and resistance forces that help the cell to migrate....
6.9K
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
Cell Migration01:09

Cell Migration

Cell migration, the process by which cells move from one location to another, is essential for the proper development and viability of organisms throughout their life. When cells are not able to migrate properly to their ordained locations, various disorders may occur. For example, disruption in cell migration causes chronic inflammatory diseases such as arthritis.
18.9K
Cell Migration01:19

Cell Migration

Cell migration is a process by which the cells move from one location to another, playing an essential role in embryological development, repair and regeneration, immune response, and metastasis. Cells migrate in response to chemical or mechanical signals generated by specific organs or tissues. The overall mechanism includes three steps - polarization, protrusion, and release. Polarization involves the formation of a distinct cell front and rear, which determines the direction of movement.
6.8K