Tumor-Derived Fibronectin Is Involved in Melanoma Cell Invasion and Regulated by V600E B-Raf Signaling Pathway
| Autor: | Philippe Bahadoran, Corine Bertolotto, Véronique Baron, Olivier Bailet, Robert Ballotti, Jean-Paul Ortonne, Guillaume Robert, Cedric Gaggioli, Sophie Tartare-Deckert, Patricia Abbe, Anne Spadafora |
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| Rok vydání: | 2007 |
| Předmět: |
MAPK/ERK pathway
Proto-Oncogene Proteins B-raf Small interfering RNA Glutamic Acid Dermatology medicine.disease_cause Biochemistry 03 medical and health sciences 0302 clinical medicine medicine Humans Neoplasm Invasiveness Extracellular Signal-Regulated MAP Kinases Melanoma Molecular Biology Cells Cultured 030304 developmental biology Early Growth Response Protein 1 0303 health sciences biology Valine Cell Biology medicine.disease 3. Good health Fibronectins Fibronectin Enzyme Activation Tumor progression 030220 oncology & carcinogenesis Mitogen-activated protein kinase Mutation biology.protein Cancer research Disease Progression Melanocytes Signal transduction Carcinogenesis Signal Transduction |
| Zdroj: | Journal of Investigative Dermatology. 127(2):400-410 |
| ISSN: | 0022-202X |
| DOI: | 10.1038/sj.jid.5700524 |
| Popis: | Melanomas are malignant tumors of melanocytes that, if not detected early, are highly aggressive and poorly treatable. Activation of extracellular signal-regulated (ERK)/mitogen-activated protein (MAP) kinase signaling is commonly found in melanomas mainly through oncogenic mutations of B-Raf. We previously reported that activation of ERK/MAP kinase stimulates synthesis of fibronectin by upregulating the transcription factor early growth response-1 (Egr-1). To further analyze the link between ERK/MAP kinase pathway and fibronectin in melanoma, we have studied the regulation and role of fibronectin produced by melanoma cells bearing oncogenic B-Raf mutation. We show that fibronectin is expressed in situ during tumor progression and that high fibronectin and Egr-1 levels are found in cells expressing this mutation. Expression of active mutants of B-Raf induces fibronectin, whereas endogenous fibronectin is inhibited by small interfering RNA (siRNA)-mediated depletion of B-Raf or Egr-1. In contrast, stimulation of ERK pathway is insufficient to promote fibronectin upregulation in normal melanocytes. Finally, we show that suppression of fibronectin by siRNA leads to decreased melanoma cell invasiveness in vitro. These results reveal a tumor-specific regulation of fibronectin by constitutive ERK/MAP kinase signaling and indicate that self-production of fibronectin may play a role in melanoma tumorigenesis, by promoting tumor cell invasion. |
| Databáze: | OpenAIRE |
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