Contact Inhibition in Colony Formation

Fisher, Harold W.; Yeh, Jen

doi:10.1126/science.155.3762.581

Cited by 97 publications

(46 citation statements)

References 7 publications

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“…Up-regulation of Merlin by Serum Starvation and Confluency-Given Merlin's localization to the cell periphery and its status as tumor suppressor, we were interested in whether the regulation of the protein might be affected by cell-cell contact, which can result in growth inhibition of untransformed cells, as first described in NIH3T3 cells (26). NIH3T3 cells were plated at increasing degrees of confluency ( Fig.…”

Section: Resultsmentioning

confidence: 99%

Regulation of the Neurofibromatosis Type 2 Tumor Suppressor Protein, Merlin, by Adhesion and Growth Arrest Stimuli

Shaw

McClatchey

Jacks³

1998

Journal of Biological Chemistry

119

116

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Section: Resultsmentioning

confidence: 99%

Regulation of the Neurofibromatosis Type 2 Tumor Suppressor Protein, Merlin, by Adhesion and Growth Arrest Stimuli

Shaw

McClatchey

Jacks³

1998

Journal of Biological Chemistry

119

116

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“…The downregulation of Necl-5 impairs the integrin ␣ v ␤ 3 -and plateletderived growth factor receptor-dependent intracellular signaling for cell movement and proliferation, resulting in the reduction of cell movement and proliferation. The phenomenon that moving and proliferating normal cultured cells arrest both movement and proliferation after they grow confluent and form cell-cell junctions has been well known for a long time (11,12), but its molecular mechanism is poorly understood. The down-regulation of Necl-5 is likely to be at least partly one of the underlying mechanisms of contact inhibition of cell movement and proliferation.…”

mentioning

confidence: 99%

Involvement of Nectin in Inactivation of Integrin αvβ3 after the Establishment of Cell-Cell Adhesion

Sakamoto

Ogita

Komura

et al. 2008

Journal of Biological Chemistry

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Integrin plays an essential role in the formation of cell-matrix junctions and is also involved in the fundamental cellular functions. In the process of the formation of cell-cell junctions, an immunoglobulin-like cell-cell adhesion molecule nectin initially trans-interacts together and promotes the formation of adherens junctions (AJs) cooperatively with another cell-cell adhesion molecule cadherin. The activation of integrin ␣ v ␤ 3 is critically necessary for this nectin-induced formation of AJs. However, after the establishment of AJs, integrin ␣ v ␤ 3 becomes inactive and retains the association with nectin at AJs. The molecular mechanism of this dynamic regulation of integrin ␣ v ␤ 3 during the formation of AJs remains unclear. We found here that the expression of phosphatidylinositol-phosphate kinase type I␥90 (PIPKI␥90), which is involved in the regulation of integrin activation, in Madin-Darby canine kidney cells, preferentially reversed the inactivation of integrin ␣ v ␤ 3 at cell-cell adhesion sites and partially disrupted E-cadherin-based AJs. The activation of PIPKI␥ is correlated with its phosphorylation state. The tyrosine phosphatase protein-tyrosine phosphatase (PTP) effectively dephosphorylated PIPKI␥ and thus canceled the PIPKI␥-dependent activation of integrin ␣ v ␤ 3 by blocking the interaction of integrin ␣ v ␤ 3 with talin. Moreover, PTP associated with nectin, and its phosphatase activity was enhanced by the trans-interaction of nectin, leading to the decrease in PIPKI␥90 phosphorylation. Therefore, the transinteraction of nectin essentially functions in the inactivation of integrin at AJs through the PTP-induced inactivation of PIPKI␥.Integrin is a key cell-cell adhesion molecule at cell-matrix junctions and comprises heterodimers with ␣ and ␤ subunits (1). Integrin exhibits intracellular conformational changes between the low and high affinity forms (2). The low affinity form shows weak adhesion activity for extracellular matrix proteins and is inactive, whereas the high affinity form has increased adhesion activity for its extracellular ligands and is active (3). It was reported that integrin is essential for the formation of specialized subcellular apparatuses, such as focal complexes and focal adhesions, and for cell movement, proliferation, and differentiation (1, 4, 5). We recently demonstrated that integrin ␣ v ␤ 3 interacts with Necl-5 at the leading edge of moving cells and that this complex enhances cell movement and proliferation together with platelet-derived growth factor receptor by stimulation of platelet-derived growth factor (6, 7). Necl-5 is an Ig-like cell adhesion molecule and resembles nectin in its structure: three Ig-like loops at the extracellular region, a single transmembrane domain, and one cytoplasmic region.When moving cells collide with each other, the initial cellcell contact occurs with the trans-interaction of Necl-5 with nectin-3 (8). Nectin is an emerging Ig-like cell-cell adhesion molecule that localizes at adherens junctions (AJs) 2 and is involved in...

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“…This interaction then causes the down-regulation of Necl-5 by its endocytosis and eventually stops proliferation and movement. This is one of the mechanisms of so-called contact inhibition of cell movement and proliferation (14,15). The PDGF receptor and integrin ␣ v ␤ 3 remain on the plasma membrane and then may form a complex with nectin-1 and/or nectin-3, finally recruiting N-cadherin to form AJs (13).…”

mentioning

confidence: 99%

Cooperative Role of Nectin-Nectin and Nectin-Afadin Interactions in Formation of Nectin-based Cell-Cell Adhesion

Kurita

Ogita²,

Takai

2011

Journal of Biological Chemistry

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The nectin cell adhesion molecules interact in trans with each other through their extracellular regions and with afadin through their cytoplasmic tails, forming adherens junctions in cooperation with cadherins. In a single cell, Necl-5 (nectin-like molecule-5) localizes at the leading edge and regulates directional cell movement in response to a chemoattractant. In such a single cell, afadin also localizes at the leading edge without interacting with nectins or Necl-5. It remains unknown how the nectin-nectin and nectin-afadin interactions are initiated when moving cells contact each other to initiate the formation of adherens junctions. We show here that the Necl-5-nectin interaction induced by cell-cell contact enhances the nectin-afadin interaction. This interaction then enhances the nectin-nectin interaction, which further enhances the nectin-afadin interaction in a positive feedback manner. Thus, the Necl-5-nectin, nectin-nectin, and nectin-afadin interactions cooperatively increase the clustering of the nectin-afadin complex at the cellcell contact sites, promoting the formation of the nectin-based cell-cell adhesion.

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Contact Inhibition in Colony Formation

Cited by 97 publications

References 7 publications

Regulation of the Neurofibromatosis Type 2 Tumor Suppressor Protein, Merlin, by Adhesion and Growth Arrest Stimuli

Regulation of the Neurofibromatosis Type 2 Tumor Suppressor Protein, Merlin, by Adhesion and Growth Arrest Stimuli

Involvement of Nectin in Inactivation of Integrin αvβ3 after the Establishment of Cell-Cell Adhesion

Cooperative Role of Nectin-Nectin and Nectin-Afadin Interactions in Formation of Nectin-based Cell-Cell Adhesion

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