期刊
JOURNAL OF BIOLOGICAL CHEMISTRY
卷 283, 期 30, 页码 20770-20778出版社
AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
DOI: 10.1074/jbc.M709892200
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资金
- NCI NIH HHS [CA 124488, CA 100035, CA 46565] Funding Source: Medline
- NHLBI NIH HHS [HL 081390] Funding Source: Medline
- NIA NIH HHS [R01 AG021842, AG 21842, R01 AG021842-05] Funding Source: Medline
- NIDDK NIH HHS [DK 68503, R01 DK044525-14, R01 DK054687-09, DK 54687, R01 DK056283-04, R01 DK056283, R01 DK044525, R01 DK054687, DK 44525] Funding Source: Medline
The Forkhead box M1 (FoxM1) protein is a proliferation-specific transcription factor that plays a key role in controlling both the G(1)/S and G(2)/M transitions through the cell cycle and is essential for the development of various cancers. We show here that FoxM1 directly activates the transcription of the c-Jun N-terminal kinase (JNK1) gene in U2OS osteosarcoma cells. Expression of JNK1, which regulates the expression of genes important for the G(1)/S transition, rescues the G(1)/S but not the G(2)/M cell cycle block in FoxM1-deficient cells. Knockdown of either FoxM1 or JNK1 inhibits tumor cell migration, invasion, and anchorage-independent growth. However, expression of JNK1 in FoxM1-depleted cells does not rescue these defects, indicating that JNK1 is a necessary but insufficient downstream mediator of FoxM1 in these processes. Consistent with this interpretation, FoxM1 regulates the expression of the matrix metalloproteinases MMP-2 and MMP-9, which play a role in tumor cell invasion, through JNK1-independent and -dependent mechanisms in U2OS cells, respectively. Taken together, these findings identify JNK1 as a critical transcriptional target of FoxM1 that contributes to FoxM1-regulated cell cycle progression, tumor cell migration, invasiveness, and anchorage-independent growth.
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