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Event: 1241

Key Event Title

A descriptive phrase which defines a discrete biological change that can be measured. More help

Increased, Motility

Short name
The KE short name should be a reasonable abbreviation of the KE title and is used in labelling this object throughout the AOP-Wiki. More help
Increased, Motility
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Biological Context

Structured terms, selected from a drop-down menu, are used to identify the level of biological organization for each KE. More help
Level of Biological Organization
Cellular

Cell term

The location/biological environment in which the event takes place.The biological context describes the location/biological environment in which the event takes place.  For molecular/cellular events this would include the cellular context (if known), organ context, and species/life stage/sex for which the event is relevant. For tissue/organ events cellular context is not applicable.  For individual/population events, the organ context is not applicable.  Further information on Event Components and Biological Context may be viewed on the attached pdf. More help
Cell term
eukaryotic cell

Organ term

The location/biological environment in which the event takes place.The biological context describes the location/biological environment in which the event takes place.  For molecular/cellular events this would include the cellular context (if known), organ context, and species/life stage/sex for which the event is relevant. For tissue/organ events cellular context is not applicable.  For individual/population events, the organ context is not applicable.  Further information on Event Components and Biological Context may be viewed on the attached pdf. More help

Key Event Components

The KE, as defined by a set structured ontology terms consisting of a biological process, object, and action with each term originating from one of 14 biological ontologies (Ives, et al., 2017; https://aopwiki.org/info_pages/2/info_linked_pages/7#List). Biological process describes dynamics of the underlying biological system (e.g., receptor signalling).Biological process describes dynamics of the underlying biological system (e.g., receptor signaling).  The biological object is the subject of the perturbation (e.g., a specific biological receptor that is activated or inhibited). Action represents the direction of perturbation of this system (generally increased or decreased; e.g., ‘decreased’ in the case of a receptor that is inhibited to indicate a decrease in the signaling by that receptor).  Note that when editing Event Components, clicking an existing Event Component from the Suggestions menu will autopopulate these fields, along with their source ID and description.  To clear any fields before submitting the event component, use the 'Clear process,' 'Clear object,' or 'Clear action' buttons.  If a desired term does not exist, a new term request may be made via Term Requests.  Event components may not be edited; to edit an event component, remove the existing event component and create a new one using the terms that you wish to add.  Further information on Event Components and Biological Context may be viewed on the attached pdf. More help
Process Object Action
cell motility increased

Key Event Overview

AOPs Including This Key Event

All of the AOPs that are linked to this KE will automatically be listed in this subsection. This table can be particularly useful for derivation of AOP networks including the KE.Clicking on the name of the AOP will bring you to the individual page for that AOP. More help
AOP Name Role of event in AOP Point of Contact Author Status OECD Status
ER activation to breast cancer KeyEvent Brendan Ferreri-Hanberry (send email) Open for adoption
AhR activation to metastatic breast cancer KeyEvent Evgeniia Kazymova (send email) Under Development: Contributions and Comments Welcome Under Development

Taxonomic Applicability

Latin or common names of a species or broader taxonomic grouping (e.g., class, order, family) that help to define the biological applicability domain of the KE.In many cases, individual species identified in these structured fields will be those for which the strongest evidence used in constructing the AOP was available in relation to this KE. More help
Term Scientific Term Evidence Link
Homo sapiens Homo sapiens High NCBI

Life Stages

An indication of the the relevant life stage(s) for this KE. More help
Life stage Evidence
Adult High

Sex Applicability

An indication of the the relevant sex for this KE. More help
Term Evidence
Female High
Male High

Key Event Description

A description of the biological state being observed or measured, the biological compartment in which it is measured, and its general role in the biology should be provided. More help

Cell motility is the capacity of cells to translocate onto a solid substratum.

In order to move several actions such as : cell–substrate adhesion, cell–cell adhesion, cell cortex rigidity (membrane and cytoskeleton), actin polymerization-mediated protrusion and actomyosin contractility (Stuelten, Lauffenburger, Montell).

Several key factors contribute to cell motility in cancer (Friedl, Lamouille, Sahail):

  • Actin Cytoskeleton Dynamics: The actin cytoskeleton plays a crucial role in cell motility. Remodeling of the actin cytoskeleton is essential for cell shape changes, protrusion formation, and cell migration. This process is tightly regulated by proteins such as actin polymerization factors, focal adhesion proteins, and myosin motors.
  • Cell Adhesion and Extracellular Matrix (ECM) Interactions: Integrins and other cell adhesion molecules mediate the interaction between cancer cells and the ECM. These interactions activate signaling pathways that influence cell motility. Changes in adhesion molecules can enhance or inhibit the migratory potential of breast cancer cells.
  • Epithelial-Mesenchymal Transition (EMT): EMT is a biological process in which epithelial cells acquire mesenchymal characteristics, including increased motility. EMT is associated with the invasive behavior of cancer cells, allowing them to detach from the primary tumor and migrate to distant sites.
  • Chemotaxis and Gradients: Cancer cells can respond to chemical gradients, a process known as chemotaxis. Growth factors and cytokines in the tumor microenvironment can attract or repel cancer cells, influencing their direction of movement.
  • Proteolytic Enzymes and Matrix Metalloproteinases (MMPs): Proteolytic enzymes, especially MMPs, are involved in degrading the ECM, facilitating cancer cell invasion. The degradation of the surrounding matrix creates space for cell movement and allows cancer cells to penetrate adjacent tissues.

In breast cancer, cell motility can favor metastasis through different steps: loss of epithelial polarity, breakdown of tissue architecture, breach of the basement membrane, intravasation, extravasation, migration into new tissues, and expansion of metastatic colonies (Stuelten). For instance, an increase in invasion of the surrounding tissues and blood vessels. Once cancer cells have invaded the local tissue, they may enter the bloodstream through a process called intravasation. Subsequently, they must migrate through the vasculature to reach distant organs, a process known as extravasation (Chambers). Once in the circulation, cells utilize chemotaxis, responding to chemokines and other signals in the microenvironment, to navigate through the bloodstream and reach specific distant organs. The ability of cancer cells to home in on specific organs depends on their motility and the interactions with the target tissue (Psaila, Labelle). Once cancer cells reach a distant organ, they need to extravasate and establish micrometastases. Motility enables cancer cells to navigate through the tissue, invade the local environment, and form secondary tumor foci (Nguyen).

How It Is Measured or Detected

A description of the type(s) of measurements that can be employed to evaluate the KE and the relative level of scientific confidence in those measurements.These can range from citation of specific validated test guidelines, citation of specific methods published in the peer reviewed literature, or outlines of a general protocol or approach (e.g., a protein may be measured by ELISA). Do not provide detailed protocols. More help

Several assays can be used to measure cell motility, and the choice depends on the specific requirements and characteristics of the cells being studied. Here are some commonly used assays for measuring cell motility (Justus)

  • Wound Healing Assay (Scratch Assay):

Principle: Create a controlled "wound" or scratch in a cell monolayer and monitor the closure of the gap over time.

Measurement: Quantify the rate of cell migration by measuring the reduction in the wound area.

  • Transwell Migration Assay:

Principle: Cells migrate through a porous membrane from one side to the other in response to a chemoattractant.

Measurement: Count the number of cells that have migrated through the membrane or quantify fluorescence if cells are labeled.

  • Boyden Chamber Assay:

Principle: Similar to the Transwell assay, cells migrate through a membrane towards a chemoattractant.

Measurement: Assess the migrated cells on the lower surface of the membrane.

  • Time-Lapse Microscopy:

Principle: Track the movement of individual cells over time using live-cell imaging.

Measurement: Analyze cell trajectories, speed, and directionality.

  • Collagen Invasion Assay:

Principle: Assess cell invasion through a three-dimensional collagen matrix.

Measurement: Quantify the extent of cell invasion into the matrix

  • Fluorescence Recovery After Photobleaching (FRAP):

Principle: Measure the mobility of fluorescently labeled molecules or proteins within cells.

Measurement: Assess the recovery of fluorescence in a photobleached region over time.

  • Single-Cell Tracking:

Principle: Monitor individual cell movements using time-lapse microscopy.

Measurement: Analyze parameters such as speed, persistence, and directionality for each tracked cell.

  • Electric Cell-Substrate Impedance Sensing (ECIS):

Principle: Measure changes in electrical impedance as cells migrate and interact with a substrate.

Measurement: Quantify impedance-based parameters to assess cell motility.

  • Bead-Based Motility Assay:

Principle: Attach beads to cells and track their movement using microscopy.

Measurement: Analyze the displacement of beads to determine cell motility.

Selecting the most appropriate assay depends on factors such as the nature of the cells, the desired readout, and the specific aspects of cell motility being investigated. Researchers often use a combination of these assays to gain a comprehensive understanding of cell motility in different contexts

Domain of Applicability

A description of the scientific basis for the indicated domains of applicability and the WoE calls (if provided).  More help

Cell motility has been largely described in human breast cancer cell lines, mice and fish (Stuelten)

References

List of the literature that was cited for this KE description. More help

Stuelten, C., Parent, C. & Montell, D. Cell motility in cancer invasion and metastasis: insights from simple model organisms. Nat Rev Cancer 18, 296–312 (2018). https://doi.org/10.1038/nrc.2018.15

Justus CR, Leffler N, Ruiz-Echevarria M, Yang LV. In vitro cell migration and invasion assays. J Vis Exp. 2014 Jun 1;(88):51046. doi: 10.3791/51046. PMID: 24962652; PMCID: PMC4186330.

Lauffenburger DA, Horwitz AF. Cell migration: a physically integrated molecular process. Cell. 1996 Feb 9;84(3):359-69. doi: 10.1016/s0092-8674(00)81280-5. PMID: 8608589.

Chambers, A. F., Groom, A. C., & MacDonald, I. C. (2002). Dissemination and growth of cancer cells in metastatic sites. Nature Reviews Cancer, 2(8), 563–572. doi:10.1038/nrc865

Montell DJ. Morphogenetic cell movements: diversity from modular mechanical properties. Science. 2008 Dec 5;322(5907):1502-5. doi: 10.1126/science.1164073. PMID: 19056976.

Friedl, P., & Wolf, K. (2003). Tumour-cell invasion and migration: diversity and escape mechanisms. Nature Reviews Cancer, 3(5), 362–374. doi:10.1038/nrc1075

Lamouille, S., Xu, J., & Derynck, R. (2014). Molecular mechanisms of epithelial-mesenchymal transition. Nature Reviews Molecular Cell Biology, 15(3), 178–196. doi:10.1038/nrm3758

Sahai, E. (2005). Mechanisms of cancer cell invasion. Current Opinion in Genetics & Development, 15(1), 87–96. doi:10.1016/j.gde.2004.12.002

Psaila, B., & Lyden, D. (2009). The metastatic niche: adapting the foreign soil. Nature Reviews Cancer, 9(4), 285–293. doi:10.1038/nrc2621

Labelle, M., & Hynes, R. O. (2012). The initial hours of metastasis: the importance of cooperative host-tumor cell interactions during hematogenous dissemination. Cancer Discovery, 2(12), 1091–1099. doi:10.1158/2159-8290.CD-12-0329

Nguyen, D. X., & Bos, P. D. (2009). Massagué, J. (2009). Metastasis: from dissemination to organ-specific colonization. Nature Reviews Cancer, 9(4), 274–284. doi:10.1038/nrc2622

Quail, D. F., & Joyce, J. A. (2013). Microenvironmental regulation of tumor progression and metastasis. Nature Medicine, 19(11), 1423–1437. doi:10.1038/nm.3394