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Spatially and temporally regulated membrane complexes in cancer cell invasion and cytokinesis

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Integrins in metastasis

Metastasis — the migration and invasion of cancer cells to distant organs or tissues — is a hallmark of cancer progression. Identification of the mechanism responsible for initiation of metastasis should lead to novel therapies.

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Integrins are transmembrane cell surface adhesion molecules that regulate many key cellular processes including division and motility. Emerging evidence is pointing towards a role for integrins in carcinogenesis and especially metastasis. The EU-funded CANCER SIGNALOSOMES (Spatially and temporally regulated membrane complexes in cancer cell invasion and cytokinesis) project set out to delineate the mechanism by which integrins may be implicated in cancer. Their work focused in particular on the dynamic integrin signalosomes at the leading edge of invading cells. Scientists believe that these signalosomes dictate the movement of cancer cells. The consortium used several novel and cutting-edge approaches such as RNA interference, live-cell arrays and proteomics. This helped them analyse the functional complexes recruited to integrins in cancer cells and the pathways involved in integrin regulation. They identified several integrin binding partners that are key players in cell motility and metastasis. They also demonstrated that cell adhesion was vital for normal cell division and the maintenance of genome integrity. In addition, they identified novel molecular interactions of integrin regulation in human cancer. Overall, the activities of the CANCER SIGNALOSOMES project provided important mechanistic insight into cancer metastasis by unravelling new integrin functions. These findings increase our understanding of cancer progression and have the potential to lead to new interventions targeting both cancer proliferation and dissemination in the body.

Keywords

Integrin, metastasis, cancer, signalosome, cell adhesion

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