期刊
CANCER BIOLOGY & THERAPY
卷 18, 期 1, 页码 8-15出版社
TAYLOR & FRANCIS INC
DOI: 10.1080/15384047.2016.1250984
关键词
GLUT4; glucose metabolism; melanoma; metastasis; proliferation; TDP-43
类别
资金
- National Natural Science Foundation of China [81572689, 81372140, 81301688, 81272192, 81171882]
- PhD. Programs Foundation of Ministry of Education of China [20130162110050, 20130162120093]
- Natural Science Foundation of Hunan Province [2015JJ4053, 2016JJ6154]
- Project of Science and Technology of Hunan Province [2014SK2018, 2015SF2066-2]
- Program for New Century Excellent Talents in University [NCET-11-0527]
- Postdoctoral Foundation of Central South University [131425]
- Third Xiangya Hospital of Central South University
- New Xiangya Talent Projects of the Third Xiangya Hospital of Central South University [JY201623]
Background: Although recent studies have revealed TAR (trans-activating response region) DNA binding protein (TDP-43) as a potential therapeutic target for cancers, its role and clinical association with melanoma have not been explored. Objective: To identify the role and function of TDP-43 during melanoma pathogenesis. Methods: Firstly, the relationship between TDP-43 expression and patient survival was explored. Then TDP-43 expression level in melanoma tissue and different melanoma cell lines was measured. After silencing TDP-43 expression in melanoma cells, the impacts of TDP-43 on cellular proliferation, metastasis, glucose uptake, and glucose transporters levels were studied. In the end, effect of TDP-43 depletion on tumorigenicity of melanoma cells was tested in vivo. Results: Our results showed that TDP-43 was overexpressed in melanoma paraffin samples compared with that in nevi tissues. The high expression level of TDP-43 was associated with poor patient survival. By silencing TDP-43, we saw significant inhibition of cell proliferation and metastasis in A375 and WM451 cells. TDP-43 knockdown could suppress glucose transporter type-4 (GLUT4) expression and reduce glucose uptake. And downregulation of GLUT4 in melanoma cells induced inhibition of cell proliferation and metastasis. TDP-43 knockdown significantly slowed down tumor growth and decreased GLUT4 expression in vivo. Conclusion: TDP-43 is a novel oncogene in melanoma and regulates melanoma proliferation and metastasis potentially through modulation of glucose metabolism.
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