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. 2010 Nov 15;286(2):1475–1485. doi: 10.1074/jbc.M110.127522

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© 2011 by The American Society for Biochemistry and Molecular Biology, Inc.

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FIGURE 8. — Proposed model for V3-mediated effects in MeWo melanoma cells. Left, CD44 and the ErbB2/EGFR complex are main signaling pathways in MeWo melanoma cells, leading to tumor cell growth and migration. CD44 also regulates HA catabolism by regulating HYAL2 activity and allowing HA internalization. Right, in V3-expressing cells, V3 interferes with HA-CD44-EGFR/ErbB2 interaction through its G1 and G3 domains, leading to a delayed activation of EGFR-mediated signaling pathways, such as ERK1/2 and p38 MAPK. CD44-dependent mechanisms, such as hyaluronan internalization and HYAL2 activity, are inhibited. Cell proliferation and migration on plastic are decreased due to impairment of both transduction pathways. Nevertheless, adhesion and migration on HA-coated surfaces are enhanced because of the accumulation of HA and the presence of CD44.