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| Content Provider | PubMed Central |
|---|---|
| Author | Grahovac, Jelena Becker, Dorothea Wells, Alan |
| Abstract | Tenascin-C (TNC), overexpressed in invasive growths, has been implicated in progression of melanoma but the source and function of this molecule are not well defined. We found TNC expression at the front of invading melanoma cells, and that adding TNC to matrices enhances individual melanoma cell migration. As TNC is a multidomain protein, we examined the role of the TNC EGF-like repeats (EGFL) as these activate motogenic signaling cascades. We overexpressed a TNC fragment containing the assembly and EGFL domains of TNC (TNCEGFL). TNCEGFL-expressing melanoma cells had lower speed and persistence in 2D migration assays due to a shift in the adhesion-contractility balance, as expression of TNCEGFL delayed melanoma cell attachment and spreading. The less adhesive phenotype was due, in part, to increased ROCK signaling concomitant with MLC2 and MYPT phosphorylation. Inhibition of ROCK activity, which drives transcellular contractility, restored adhesion of TNCEGFL expressing melanoma cells and increased their migration in 2D. In contrast to the diminished migration in 2D, TNCEGFL-expressing melanoma cells had higher invasive potential in Matrigel invasion assays, with cells expressing TNCEGFL having amoeboid morphology. Our findings suggest that melanoma-derived TNC EGFL play a role in melanoma invasion by modulating ROCK signaling and cell migration. |
| Related Links | http://dx.doi.org/10.1038/jid.2012.263 |
| Ending Page | 220 |
| Page Count | 11 |
| Starting Page | 210 |
| File Format | |
| ISSN | 0022202X |
| e-ISSN | 15231747 |
| Journal | The Journal of investigative dermatology |
| Issue Number | 1 |
| Volume Number | 133 |
| Language | English |
| Publisher Date | 2013-01-01 |
| Access Restriction | Open |
| Subject Keyword | Cell Biology Biochemistry Molecular Biology Dermatology Research in Higher Education |
| Content Type | Text |
| Resource Type | Article |
| Subject | Cell Biology Biochemistry Molecular Biology Dermatology |
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