Yang, Pei-Tzu and Anastas, Jamie N. and Toroni, Rachel A. and Shinohara, Michi M. and Goodson, Jamie M. and Bosserhoff, Anja K. and Chien, Andy J. and Moon, Randall T. (2012) WLS inhibits melanoma cell proliferation through the ss-catenin signalling pathway and induces spontaneous metastasis. EMBO MOLECULAR MEDICINE, 4 (12). pp. 1294-1307. ISSN 1757-4676, 1757-4684
Full text not available from this repository. (Request a copy)Abstract
Elevated levels of nuclear beta-catenin are associated with higher rates of survival in patients with melanoma, raising questions as to how beta-catenin is regulated in this context. In the present study, we investigated the formal possibility that the secretion of WNT ligands that stabilize beta-catenin may be regulated in melanoma and thus contributes to differences in beta-catenin levels. We find that WLS, a conserved transmembrane protein necessary for WNT secretion, is decreased in both melanoma cell lines and in patient tumours relative to skin and to benign nevi. Unexpectedly, reducing endogenous WLS with shRNAs in human melanoma cell lines promotes spontaneous lung metastasis in xenografts in mice and promotes cell proliferation in vitro. Conversely, overexpression of WLS inhibits cell proliferation in vitro. Activating beta-catenin downstream of WNT secretion blocks the increased cell migration and proliferation observed in the presence of WLS shRNAs, while inhibiting WNT signalling rescues the growth defects induced by excess WLS. These data suggest that WLS functions as a negative regulator of melanoma proliferation and spontaneous metastasis by activating WNT/beta-catenin signalling.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | NEVUS-ASSOCIATED MELANOMAS; WNT-PRODUCING CELLS; BETA-CATENIN; MALIGNANT-MELANOMA; CUTANEOUS MELANOMA; EXPRESSION; PROGRESSION; SECRETION; WNTLESS; DISEASE; beta-catenin; melanoma; spontaneous metastasis; WNTLESS; WNT secretion |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Pathologie |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 04 May 2020 05:53 |
| Last Modified: | 04 May 2020 05:53 |
| URI: | https://pred.uni-regensburg.de/id/eprint/17671 |
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