1.17 Cancer Cell Adhesion Foundations

Cancer Cell Adhesion Foundations is a description of the collection of core concepts underlying how cancer cells attach to, detach from, and interact with neighboring cells and the surrounding extracellular environment, and how alterations to these adhesive processes, relative to their normal operation in non-cancerous cells, contribute to the characteristic behaviors of cancer cells, including their capacity to invade surrounding tissue and disseminate to distant sites. Cell adhesion encompasses the molecular mechanisms through which cells physically attach to other cells and to the extracellular matrix, and disruption of these mechanisms represents a foundational theme underlying cancer cell biology.

Conceptual Basis

Adhesion as a Structural and Signaling System

Cell adhesion functions both as a structural system, physically anchoring a cell to its neighbors or to the surrounding extracellular matrix, and as a signaling system, since adhesive contacts commonly generate intracellular signals that influence a wide range of cellular behaviors beyond simple physical attachment, including proliferation and survival.

Relevance to Cancer Cell Biology

Because normal tissue architecture depends on cells maintaining appropriate adhesive relationships with their neighbors and their surrounding matrix, alterations affecting adhesion are closely linked to the loss of normal tissue organization and the capacity for invasive and disseminated growth observed in cancer cells, positioning adhesion disruption as a foundational theme running throughout cancer cell biology.

Core Components

Cell-Cell Adhesion Molecules

Cell-cell adhesion molecules are proteins positioned at the surface of a cell that mediate direct physical attachment to corresponding molecules on the surface of an adjacent cell, establishing and maintaining contact between neighboring cells within a tissue.

Cell-Matrix Adhesion Molecules

Cell-matrix adhesion molecules are proteins positioned at the cell surface that mediate physical attachment between a cell and the surrounding extracellular matrix, anchoring the cell within its local structural environment rather than to another cell directly.

Adhesion-Associated Signaling

Adhesive contacts, whether cell-cell or cell-matrix, are commonly coupled to intracellular signaling activity, such that the physical state of a cell's adhesive contacts, including their presence, strength, and type, influences signaling pathways governing proliferation, survival, and other aspects of cellular behavior.

Regulation of Adhesive Strength and Turnover

Cell adhesion is subject to regulatory mechanisms governing the strength of existing adhesive contacts and the rate at which such contacts are formed and disassembled, allowing a cell to dynamically adjust its adhesive relationships in accordance with its current functional requirements.

Relationship to Cancer Cell Behavior

A Determinant of Tissue Organization and Cell Mobility

The overall pattern of a cell's adhesive contacts is a principal determinant of whether that cell remains stably integrated within its surrounding tissue or is instead capable of detaching and moving independently, linking the function of cell adhesion directly to the behavioral characteristics that distinguish invasive cancer cells from normal, tissue-resident cells.

A Frequent Target of Disruption

Components of the cell adhesion system, including cell-cell and cell-matrix adhesion molecules and their associated signaling and regulatory mechanisms, are frequently altered during the development of cancer cells, reflecting the close relationship between disrupted adhesion and the acquisition of invasive and disseminated growth behaviors.

Foundational Themes Within This Area

Distinguishing Cell-Cell Adhesion From Cell-Matrix Adhesion

A recurring foundational distinction within the study of cancer cell adhesion is between adhesion connecting a cell to its neighboring cells and adhesion connecting a cell to the surrounding extracellular matrix, with disruption of either category capable of independently contributing to loss of normal tissue organization, though through distinct mechanisms and with distinct consequences.

Distinguishing Adhesive Structure From Adhesive Signaling

A further foundational distinction concerns the difference between the purely structural, attachment-providing function of adhesion molecules and the separate signaling consequences that arise from the state of a cell's adhesive contacts, both of which are integrated within the broader function of cell adhesion but represent conceptually separate levels at which disruption can occur.