TGF-β is associated with poor prognosis and promotes osteosarcoma progression via PI3K/Akt pathway activation.
TGF-β is associated with poor prognosis and promotes osteosarcoma progression via PI3K/Akt pathway activation.
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DOI：
10.1080/15384101.2020.1805552
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发表时间：
2020-09
期刊：
影响因子：
--
通讯作者：
Li W
中科院分区：
文献类型：
--
作者：
Ma K;Zhang C;Li W
转化生长因子β (TGF-β)是一种多功能细胞因子，在细胞增殖和分化中具有重要作用。TGF-β在多种类型的癌症中高表达，促进肿瘤侵袭和转移。然而，TGF-β在骨肉瘤进展中的作用尚不清楚。在本研究中，我们发现TGF-β在骨肉瘤细胞和组织中高表达，并与高Ennecking期（P = 0.033）、转移和复发相关。利用siRNA （si-TGF-β）构建TGF-β下调骨肉瘤细胞系。转染si-TGF-β的细胞增殖、迁移/侵袭和集落形成能力显著降低，细胞凋亡水平升高。此外，si-TGF-β处理降低了骨肉瘤细胞的球体大小、cd133阳性细胞比例以及SOX-2、Nanog和Oct-3/4的表达。在机制上，PI3K/mTOR磷酸化被TGF-β敲除抑制。25µM LY294002 （pi3k特异性抑制剂）预处理进一步增强了si-TGF-β诱导的骨肉瘤进展抑制。综上所述，这些结果揭示了TGF-β在骨肉瘤进展和干细胞相关性状调节中的新作用，并表明TGF-β可能作为治疗骨肉瘤的治疗靶点。
Transforming growth factor beta (TGF-β) is a multifunctional cytokine with important functions in cell proliferation and differentiation. TGF-β is highly expressed in several types of cancers and promotes tumor invasion and metastasis. However, the role of TGF-β in osteosarcoma progression is poorly understood. In the present study, we found that TGF-β is highly expressed in osteosarcoma cells and tissues, and is associated with high Ennecking stage (P = 0.033), metastasis, and recurrence. TGF-β-knockdown osteosarcoma cell lines were established using siRNA (si-TGF-β). Cells transfected with si-TGF-β exhibited significantly reduced proliferation, migration/invasion, and colony formation abilities, and increased levels of cell apoptosis. In addition, si-TGF-β treatment reduced spheroid size, the ratio of CD133-positive cells, and expression of SOX-2, Nanog, and Oct-3/4 in osteosarcoma cells. Mechanistically, PI3K/mTOR phosphorylation is inhibited by TGF-β knockdown. Pretreatment with 25 µM LY294002, a PI3K-specific inhibitor, further enhanced the si-TGF-β-induced suppression of osteosarcoma progression. Taken together, these results reveal a novel role for TGF-β in osteosarcoma progression and modulation of stemness-related traits and indicate that TGF-β may be of value as a therapeutic target for the treatment of osteosarcoma.
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影响因子：
28.2
作者：
Huang, Yun-Han;Hu, Jing;Massague, Joan
通讯作者：
Massague, Joan
影响因子：
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作者：
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通讯作者：
Zhang, Qi
DOI：
10.1016/j.jsbmb.2014.04.007
发表时间：
2015-02-01
影响因子：
4.1
作者：
Atif, Fahim;Yousuf, Seema;Stein, Donald G.
通讯作者：
Stein, Donald G.
影响因子：
15.3
作者：
Song, Ruipeng;Tian, Ke;Wang, Limin
通讯作者：
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通过控制软骨细胞分化和功能中TGF-β信号传导的调节，需要骨折愈合需要IFT80。
DOI：
10.1002/jbmr.3902
发表时间：
2020-03
期刊：
Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research
影响因子：
--
作者：
Liu M;Alharbi M;Graves D;Yang S
通讯作者：
Yang S