294) However, how cancer cells acquire the ability to evade the tumor-suppressing effects of TGF-β, yet still take advantage of its tumor-promoting effects, remains elusive. |
PMID:24292682 DOI:10.1038/onc.2013.525 |
2015 Oncogene |
* MiR-106b expression determines the proliferation paradox of TGF-β in breast cancer cells. |
- TGF-β has paradoxical effects on cancer cell proliferation, as it suppresses proliferation of normal epithelial and low-invasive cancer cells, but enhances that of high-invasive cancer cells. However, how cancer cells acquire the ability to evade the tumor-suppressing effects of TGF-β, yet still take advantage of its tumor-promoting effects, remains elusive. Here, we identified miR-106b as a molecular switch to determine TGF-β effects on cell proliferation. TGF-β1 enhances the transcription of miR-106b via a promoter independent of its host gene MCM7 by activating c-jun. In high-invasive breast cancer cells, miR-106b is upregulated by TGF-β1 at a much higher level than that in normal or low-invasive cancer cells. Accumulation of miR-106b counterbalances TGF-β growth-inhibiting effects by eliminating activated retinoblastoma (RB) and results in enhanced proliferation. Furthermore, miR-106b mediates TGF-β effects on tumor growth and metastasis in breast cancer xenografts. In addition, miR-106b expression is elevated in higher stage tumors and correlated with tumor progression in breast cancer patients. These findings suggest that high level of miR-106b induced by TGF-β determines the tumor-promoting effects of TGF-β in breast cancer. |
(1)36 cells | (17)6 size | (33)3 lysis | (49)2 progression, |
(2)23 suppressor | (18)6 suppression | (34)3 onset | (50)2 recurred |
(3)22 progression | (19)6 tissue | (35)3 targeting | (51)2 recurrence |
(4)20 necrosis | (20)6 with | (36)3 to | (52)2 regression |
(5)19 *null* | (21)5 angiogenesis | (37)3 types | (53)2 response |
(6)17 growth | (22)5 initiating | (38)2 1 | (54)2 samples, |
(7)15 cell | (23)5 suppressive | (39)2 activity | (55)2 site |
(8)14 was | (24)5 volume | (40)2 burden | (56)2 size, |
(9)12 and | (25)4 model | (41)2 classification | (57)2 that |
(10)11 development | (26)4 sites | (42)2 composed | (58)2 the |
(11)11 in | (27)4 suppressors | (43)2 expression | (59)2 tissue, |
(12)11 of | (28)3 effects | (44)2 heterogeneity | (60)2 tissues |
(13)7 microenvironment | (29)3 excision | (45)2 invasion | (61)2 treatment |
(14)6 formation | (30)3 extension | (46)2 is | |
(15)6 promotion | (31)3 had | (47)2 metastasis | |
(16)6 samples | (32)3 local | (48)2 mice |
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