Platelet derived TGF-β promotes cervical carcinoma cell growth by suppressing KLF6 expression.
Platelet derived TGF-β promotes cervical carcinoma cell growth by suppressing KLF6 expression.
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血小板衍生的 TGF-β 通过抑制 KLF6 表达促进宫颈癌细胞生长
DOI：
10.18632/oncotarget.19912
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发表时间：
2017-10-20
期刊：
影响因子：
--
通讯作者：
Ming ZY
中科院分区：
文献类型：
--
作者：
He AD;Wang SP;Xie W;Song W;Miao S;Yang RP;Zhu Y;Xiang JZ;Ming ZY
原发性肿瘤微环境中的血小板在调节肿瘤生长、转移和血管生成中起关键作用，但其潜在机制尚不清楚。在这里，我们表明，血小板释放对HeLa细胞表现出增殖作用，这种作用与KLF 6表达的减少。在与洗涤的人血小板或胶原相关肽（CRP）激活的血小板释放物孵育后，HeLa宫颈肿瘤细胞系中KLF 6的表达显著降低。然而，在对照HeLa细胞和用再悬浮的活化血小板沉淀孵育的HeLa细胞之间没有观察到显著差异。血小板对HeLa细胞生长的促进作用在KLF 6沉默的HeLa细胞中被显著消除。此外，用TGF-β受体抑制剂SB 431542阻断TGF-β信号传导也可抵消血小板对HeLa细胞增殖和KLF 6表达的影响。结论：血小板源性TGF-β通过降低KLF 6的表达促进HeLa细胞增殖。KLF 6是HeLa细胞中血小板源性TGF-β信号传导的关键靶标的发现为预防和治疗宫颈癌确定了潜在的新治疗靶标。
Platelets in the primary tumor microenvironment play crucial roles in regulating tumor growth, metastasis, and angiogenesis, but the underlying mechanisms are unclear. Here, we show that platelet releasates exhibited a proliferative effect on HeLa cells, and this effect correlated with a reduction of KLF6 expression. After incubation with either washed human platelets or collagen-related peptide (CRP) activated platelet releasates, expression of KLF6 in the HeLa cervical tumor cell line was markedly reduced. However, no significant difference was observed between control HeLa cells and HeLa cells incubated with resuspended activated platelet pellet. Moreover, the platelets’ promoting effect on HeLa cell growth was significantly abolished in KLF6 silenced HeLa cells. In addition, blocking TGF-β signaling with SB431542, a TGF-β receptor inhibitor, also counteracted the effect of platelets on proliferation and KLF6 expression in HeLa cells. From these findings, we conclude that platelet derived TGF-β promotes proliferation of HeLa cells by decreasing the expression of KLF6. The discovery that KLF6 is a key target of platelet-derived TGF-β signaling in HeLa cells identifies a potential new therapeutic target for the prevention and treatment of cervical carcinoma.
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影响因子：
25.7
作者：
Kremer-Tal, Sigal;Narla, Goutham;Friedman, Scott L.
通讯作者：
Friedman, Scott L.
影响因子：
50.3
作者：
Labelle M;Begum S;Hynes RO
通讯作者：
Hynes RO
影响因子：
4.9
作者：
Dionyssiou MG;Salma J;Bevzyuk M;Wales S;Zakharyan L;McDermott JC
通讯作者：
McDermott JC
影响因子：
56.9
作者：
Narla, G;Heath, KE;Friedman, SL
通讯作者：
Friedman, SL
DOI：
10.1038/nrc3004
发表时间：
2011-03
期刊：
Nature reviews. Cancer
影响因子：
--
作者：
Gay LJ;Felding-Habermann B
通讯作者：
Felding-Habermann B