Hypoxia-driven cell motility reflects the interplay between JMY and HIF-1α

A S Coutts1, I M Pires, L Weston

  • 1Laboratory of Cancer Biology, Department of Oncology, University of Oxford, Oxon, UK.

Oncogene
|June 1, 2011
PubMed

Insights

Junction-mediating and regulatory protein (JMY) is upregulated by hypoxia-inducible factor-1α (HIF-1α). This interaction is crucial for enhancing cell motility and invasion during hypoxic stress.

Area of Science:

  • Molecular Biology
  • Cell Biology
  • Biochemistry

Background:

  • Junction-mediating and regulatory protein (JMY) is a p53 cofactor regulating p53 activity during stress.
  • JMY interacts with p300/CBP, transcriptional co-activators involved with factors like hypoxia-inducible factor-1α (HIF-1α).
  • JMY functions as an actin-nucleating protein, promoting cell motility via its WH2 domains.

Purpose of the Study:

  • To investigate the regulation of JMY during hypoxia.
  • To determine the role of JMY in hypoxia-induced cell motility and invasion.
  • To elucidate the interplay between JMY and HIF-1α in cellular responses to hypoxic stress.

Main Methods:

  • Analyzing JMY gene promoter for HIF-responsive elements.
  • Assessing HIF-1α recruitment to the JMY promoter under hypoxia.
  • Measuring JMY expression levels during hypoxic conditions.
  • Evaluating cell motility and invasion upon JMY depletion under hypoxia.

Main Results:

  • JMY is upregulated during hypoxia in a HIF-1α-dependent manner.
  • HIF-1α binds to the JMY promoter, driving its transcription.
  • Hypoxia-induced cell motility and invasion are dependent on JMY.
  • Depletion of JMY significantly reduces cell motility under hypoxic conditions.

Conclusions:

  • Establishes a novel mechanism where JMY and HIF-1α interplay to control cell motility under hypoxic stress.
  • Highlights JMY as a key mediator of cellular adaptation to hypoxia.
  • Provides insights into the regulation of cell motility in response to environmental stress.

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. It is...
Cell Motility through Blebbing01:16

Cell Motility through Blebbing

Blebs are a type of membrane protrusion formed by the internal hydrostatic pressure of the cytoplasm. Blebs are observed in several cell types, including fibroblasts, immune cells, and single-celled organisms like the amoeba. The primary function of blebs is cell locomotion and apoptosis, but they are also found during necrosis and cell division. The life cycle of a bleb comprises an initiation phase followed by the expansion and retraction phases.
Blebbing Through the Matrix
In multicellular...
Hypoxia01:23

Hypoxia

Hypoxia is a medical condition characterized by an inadequate oxygen supply to body tissues. It typically manifests as a bluish discoloration of the skin and mucosae, especially in fair-skinned individuals, when hemoglobin (Hb) saturation drops below 75%.
Types of Hypoxia
There are four primary types of hypoxia, each resulting from a different cause:
1. Anemic hypoxia: This type occurs due to insufficient oxygen delivery caused by a lack of red blood cells (RBCs) or RBCs with abnormal or...
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.
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.
Chemotaxis and Direction of Cell Migration01:21

Chemotaxis and Direction of Cell Migration

Cells can detect chemical cues in their environment and reorganize the cytoskeleton to migrate toward them or away from them. This directional migration, called chemotaxis, is essential during embryogenesis and development, immune response, tissue repair and regeneration, and reproduction. These chemical cues can either attract or repel the cell's movement. For example, axon development is determined by a combination of chemoattractants and chemorepellents that direct the growing axon towards...