PMID- 23892595 OWN - NLM STAT- MEDLINE DCOM- 20140407 LR - 20211021 IS - 1422-0067 (Electronic) IS - 1422-0067 (Linking) VI - 14 IP - 8 DP - 2013 Jul 25 TI - Apoptosis signal-regulating kinase 1 is involved in brain-derived neurotrophic factor (BDNF)-enhanced cell motility and matrix metalloproteinase 1 expression in human chondrosarcoma cells. PG - 15459-78 LID - 10.3390/ijms140815459 [doi] AB - Chondrosarcoma is the primary malignancy of bone that is characterized by a potent capacity to invade locally and cause distant metastasis, and is therefore associated with poor prognoses. Chondrosarcoma further shows a predilection for metastasis to the lungs. The brain-derived neurotrophic factor (BDNF) is a small molecule in the neurotrophin family of growth factors that is associated with the disease status and outcome of cancers. However, the effect of BDNF on cell motility in human chondrosarcoma cells is mostly unknown. Here, we found that human chondrosarcoma cell lines had significantly higher cell motility and BDNF expression compared to normal chondrocytes. We also found that BDNF increased cell motility and expression of matrix metalloproteinase-1 (MMP-1) in human chondrosarcoma cells. BDNF-mediated cell motility and MMP-1 up-regulation were attenuated by Trk inhibitor (K252a), ASK1 inhibitor (thioredoxin), JNK inhibitor (SP600125), and p38 inhibitor (SB203580). Furthermore, BDNF also promoted Sp1 activation. Our results indicate that BDNF enhances the migration and invasion activity of chondrosarcoma cells by increasing MMP-1 expression through a signal transduction pathway that involves the TrkB receptor, ASK1, JNK/p38, and Sp1. BDNF thus represents a promising new target for treating chondrosarcoma metastasis. FAU - Lin, Chih-Yang AU - Lin CY AD - Graduate Institute of Basic Medical Science, China Medical University, Taichung 404, Taiwan. p123400@hotmail.com FAU - Chang, Sunny Li-Yun AU - Chang SL FAU - Fong, Yi-Chin AU - Fong YC FAU - Hsu, Chin-Jung AU - Hsu CJ FAU - Tang, Chih-Hsin AU - Tang CH LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20130725 PL - Switzerland TA - Int J Mol Sci JT - International journal of molecular sciences JID - 101092791 RN - 0 (Anthracenes) RN - 0 (Brain-Derived Neurotrophic Factor) RN - 0 (Carbazoles) RN - 0 (Imidazoles) RN - 0 (Indole Alkaloids) RN - 0 (Pyridines) RN - 1TW30Y2766 (pyrazolanthrone) RN - 52500-60-4 (Thioredoxins) RN - 7171WSG8A2 (BDNF protein, human) RN - 97161-97-2 (staurosporine aglycone) RN - EC 2.7.- (Protein Kinases) RN - EC 2.7.1.- (Sp1 kinase) RN - EC 2.7.10.1 (Receptor, trkB) RN - EC 2.7.11.24 (JNK Mitogen-Activated Protein Kinases) RN - EC 2.7.11.24 (p38 Mitogen-Activated Protein Kinases) RN - EC 2.7.11.25 (MAP Kinase Kinase Kinase 5) RN - EC 2.7.11.25 (MAP3K5 protein, human) RN - EC 3.4.24.7 (MMP1 protein, human) RN - EC 3.4.24.7 (Matrix Metalloproteinase 1) RN - OU13V1EYWQ (SB 203580) SB - IM MH - Anthracenes/pharmacology MH - Bone Neoplasms/*metabolism/mortality MH - Brain-Derived Neurotrophic Factor/biosynthesis/*metabolism MH - Carbazoles/pharmacology MH - Cell Line, Tumor MH - Cell Movement MH - Chondrosarcoma/*metabolism/mortality MH - Humans MH - Imidazoles/pharmacology MH - Indole Alkaloids/pharmacology MH - JNK Mitogen-Activated Protein Kinases/antagonists & inhibitors MH - MAP Kinase Kinase Kinase 5/antagonists & inhibitors/*metabolism MH - Matrix Metalloproteinase 1/biosynthesis/*metabolism MH - Neoplasm Invasiveness MH - Neoplasm Metastasis MH - Prognosis MH - Protein Kinases/metabolism MH - Pyridines/pharmacology MH - Receptor, trkB/antagonists & inhibitors MH - Signal Transduction MH - Thioredoxins/pharmacology MH - Up-Regulation MH - p38 Mitogen-Activated Protein Kinases/antagonists & inhibitors PMC - PMC3759868 EDAT- 2013/07/31 06:00 MHDA- 2014/04/08 06:00 PMCR- 2013/08/01 CRDT- 2013/07/30 06:00 PHST- 2013/05/21 00:00 [received] PHST- 2013/07/15 00:00 [revised] PHST- 2013/07/15 00:00 [accepted] PHST- 2013/07/30 06:00 [entrez] PHST- 2013/07/31 06:00 [pubmed] PHST- 2014/04/08 06:00 [medline] PHST- 2013/08/01 00:00 [pmc-release] AID - ijms140815459 [pii] AID - ijms-14-15459 [pii] AID - 10.3390/ijms140815459 [doi] PST - epublish SO - Int J Mol Sci. 2013 Jul 25;14(8):15459-78. doi: 10.3390/ijms140815459.