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  Metastasis of prostate cancer and melanoma cells in a preclinical in vivo mouse model is enhanced by L-plastin expression and phosphorylation

Riplinger, S. M., Wabnitz, G. H., Kirchgessner, H., Jahraus, B., Lasitschka, F., Schulte, B., et al. (2014). Metastasis of prostate cancer and melanoma cells in a preclinical in vivo mouse model is enhanced by L-plastin expression and phosphorylation. MOLECULAR CANCER, 13: 10. doi:10.1186/1476-4598-13-10.

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 Creators:
Riplinger, Selina M.1, Author
Wabnitz, Guido H.1, Author
Kirchgessner, Henning1, Author
Jahraus, Beate1, Author
Lasitschka, Felix1, Author
Schulte, Bianca1, Author
van der Pluijm, Gabri1, Author
van der Horst, Geertje1, Author
Haemmerling, Guenter J.1, Author
Nakchbandi, Inaam2, Author              
Samstag, Yvonne1, Author
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1external, ou_persistent22              
2Nakchbandi, Inaam / Translational Medicine, Max Planck Institute of Biochemistry, Max Planck Society, ou_1565162              

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Free keywords: PROTEIN L-PLASTIN; HUMAN T-LYMPHOCYTES; DIFFERENTIAL EXPRESSION; TUMOR-CELLS; ACTIN; INTEGRIN; ACTIVATION; MIGRATION; GROWTH; TRANSFORMATIONL-plastin; Actin cytoskeleton; Metastasis; Prostate cancer; Melanoma;
 Abstract: Background: Tumor cell migration and metastasis require dynamic rearrangements of the actin cytoskeleton. Interestingly, the F-actin cross-linking and stabilizing protein L-plastin, originally described as a leukocyte specific protein, is aberrantly expressed in several non-hematopoietic malignant tumors. Therefore, it has been discussed as a tumor marker. However, systematic in vivo analyses of the functional relevance of L-plastin for tumor cell metastasis were so far lacking. Methods: We investigated the relevance of L-plastin expression and phosphorylation by ectopical expression of L-plastin in human melanoma cells (MV3) and knock-down of endogenous L-plastin in prostate cancer (PC3M). The growth and metastatic potential of tumor cells expressing no L-plastin, phosphorylatable or non-phosphorylatable L-plastin was analyzed in a preclinical mouse model after subcutaneous and intracardial injection of the tumor cells. Results: Knock-down of endogenous L-plastin in human prostate carcinoma cells led to reduced tumor cell growth and metastasis. Vice versa, and in line with these findings, ectopic expression of L-plastin in L-plastin negative melanoma cells significantly increased the number of metastases. Strikingly, the metastasis promoting effect of L-plastin was not observed if a non-phosphorylatable L-plastin mutant was expressed. Conclusions: Our data provide the first in vivo evidence that expression of L-plastin promotes tumor metastasis and, importantly, that this effect depends on an additionally required phosphorylation of L-plastin. In conclusion, these findings imply that for determining the importance of tumor-associated proteins like L-plastin a characterization of posttranslational modifications is indispensable.

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Language(s): eng - English
 Dates: 2014
 Publication Status: Published online
 Pages: 12
 Publishing info: -
 Table of Contents: -
 Rev. Type: Peer
 Identifiers: ISI: 000331564700001
DOI: 10.1186/1476-4598-13-10
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Title: MOLECULAR CANCER
Source Genre: Journal
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Publ. Info: 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND : BIOMED CENTRAL LTD
Pages: - Volume / Issue: 13 Sequence Number: 10 Start / End Page: - Identifier: ISSN: 1476-4598