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. 2018 Jun 12;9:1277. doi: 10.3389/fimmu.2018.01277

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Copyright © 2018 Vences-Catalán and Levy.

This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

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Tetraspanins modulate invasion and metastases by regulating the activity of their partners. (A) Tetraspanins form stable lateral association with integrins in tetraspanin-enriched microdomains (TEMS) favoring spreading, cell adhesion, and migration through the extracellular matrix (ECM); on the other hand, (B) tetraspanins regulate ECM degradation during cell invasion by modulating expression and activity of metalloproteases, such as MMP-2, MMP-9, and MMP-14. (C) The TspanC8 subgroup is known to promote trafficking and cell localization of ADAM10 and its sheddase activity thereby regulating substrates, such as NOTCH receptor, to favor epithelial to mesenchymal transition (EMT). (D) Association of CD9/CD81 with EWI-2 affects TGFβ signaling modulating EMT, invasion, and metastases of melanoma.