TCTP as a therapeutic target in melanoma treatment

• Published in: British journal of cancer Vol. 117; no. 5; pp. 656 - 665
• Main Authors: Boia-Ferreira, M, Basílio, A B, Hamasaki, A E, Matsubara, F H, Appel, M H, Da Costa, C R V, Amson, R, Telerman, A, Chaim, O M, Veiga, S S, Senff-Ribeiro, A
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 22.08.2017; Nature Publishing Group; Cancer Research UK
• Subjects: 631/67/1059/153; 631/80/83; 692/4028/67/1059/153; Animals; Antineoplastic Agents, Alkylating - therapeutic use; Biomarkers, Tumor - antagonists & inhibitors; Biomarkers, Tumor - genetics; Biomarkers, Tumor - metabolism; Biomedical and Life Sciences; Biomedicine; Cancer Research; Cell Line, Tumor; Cell Movement - drug effects; Cell Proliferation - genetics; Cell Survival - drug effects; Colonies; Dacarbazine; Dacarbazine - therapeutic use; Drug Resistance; Epidemiology; Female; Gene Expression - drug effects; Gene Expression - genetics; Gene Silencing; Humans; Life Sciences; Melanoma; Melanoma - genetics; Melanoma - metabolism; Melanoma, Experimental - drug therapy; Mice; Mice, Inbred C57BL; Migration; Molecular Medicine; Oncology; p53 Protein; Phylogeny; Proteins; Reversion; RNA, Messenger - metabolism; RNA, Small Interfering - genetics; Sertraline; Sertraline - pharmacology; Sertraline - therapeutic use; siRNA; Skin Neoplasms - drug therapy; Transfection; Translational Therapeutics; Tumor Stem Cell Assay; Tumor Suppressor Protein p53 - metabolism; Tumors; Viability; melanoma; TCTP; HRF; tpt1; sertraline; dacarbazine
• ISSN: 0007-0920; 1532-1827
• DOI: 10.1038/bjc.2017.230

Background: Translationally controlled tumour protein (TCTP) is an antiapoptotic protein highly conserved through phylogeny. Translationally controlled tumour protein overexpression was detected in several tumour types. Silencing TCTP was shown to induce tumour reversion. There is a reciprocal repression between TCTP and P53. Sertraline interacts with TCTP and decreases its cellular levels. Methods: We evaluate the role of TCTP in melanoma using sertraline and siRNA. Cell viability, migration, and clonogenicity were assessed in human and murine melanoma cells in vitro . Sertraline was evaluated in a murine melanoma model and was compared with dacarbazine, a major chemotherapeutic agent used in melanoma treatment. Results: Inhibition of TCTP levels decreases melanoma cell viability, migration, clonogenicity, and in vivo tumour growth. Human melanoma cells treated with sertraline show diminished migration properties and capacity to form colonies. Sertraline was effective in inhibiting tumour growth in a murine melanoma model; its effect was stronger when compared with dacarbazine. Conclusions: Altogether, these results indicate that sertraline could be effective against melanoma and TCTP can be a target for melanoma therapy.