contactinhibited

Contact-inhibited describes cells that stop dividing when they come into contact with neighboring cells, a phenomenon known as contact inhibition of proliferation (CIP). In normal tissues, CIP helps establish and maintain a confluent, well-organized monolayer. Many non-transformed somatic cell types show CIP, while cancer cells often lose this growth constraint and continue to proliferate despite cell–cell contact.

Mechanisms involve cell–cell adhesion molecules such as E-cadherin and the cadherin–catenin complex at adherens junctions, as well as integrins that sense the surrounding matrix. At high density, signaling pathways shift to restrain the cell cycle; the Hippo pathway regulates YAP/TAZ activity, promoting cytoplasmic retention and transcriptional programs that reduce proliferation. Upstream cues include contact-dependent changes in actin organization, cell polarity, and reduced growth factor signaling, leading to accumulation of cyclin-dependent kinase inhibitors like p27Kip1 and G1 arrest.

Physiological roles include proper tissue morphogenesis, wound healing, and maintenance of tissue architecture. Loss of CIP is associated with tumorigenesis and progression, where cells acquire the ability to invade and grow beyond their neighbors. CIP can be context-dependent and vary among cell types; some cells display density-dependent arrest selectively in certain phases of the cell cycle or during differentiation.

Experimental assessment typically involves plating cells at different densities and measuring proliferation, DNA synthesis, or cell-cycle markers, along with imaging of YAP/TAZ localization and cadherin junctions.