Inhibin B suppresses anoikis resistance and migration through the transforming growth factor-β signaling pathway in nasopharyngeal carcinoma.
Inhibin B suppresses anoikis resistance and migration through the transforming growth factor-β signaling pathway in nasopharyngeal carcinoma.
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DOI：
10.1111/cas.13780
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发表时间：
2018-11
期刊：
影响因子：
5.7
通讯作者：
Zhang W
中科院分区：
文献类型：
--
作者：
Zou G;Ren B;Liu Y;Fu Y;Chen P;Li X;Luo S;He J;Gao G;Zeng Z;Xiong W;Li G;Huang Y;Xu K;Zhang W
抑制素B（INHB B）是一种由共同的α亚基和βB亚基组成的异源二聚体，是一种属于转化生长因子-β（TGF-β）家族的糖蛋白。在这项研究中，我们观察到与非肿瘤鼻咽上皮组织相比，INHBB在鼻咽癌（NPC）组织中的表达降低，并且INHBB与淋巴结转移、疾病分期和临床进展相关。INHBB阳性表达者预后较好（P = 0.038）。然而，INHBB在NPC中的分子机制尚未得到解决。我们在非锚定条件下诱导NPC细胞系中的失巢凋亡抵抗细胞，然后发现上皮-间质转化标志物改变，细胞凋亡减少，细胞周期改变，失巢凋亡抵抗的NPC细胞侵袭增强。与粘附细胞相比，这些抗失巢凋亡的NPC细胞显示INHBB表达降低。此外，发现INHBB影响上述变化。在INHBB过表达的失巢凋亡抗性NPC细胞中，凋亡细胞增加，S期细胞减弱，波形蛋白、基质金属肽酶-9和血管内皮生长因子A表达下调，E-钙粘蛋白表达上调，而在INHBB（INHBB shRNA）失巢凋亡抗性NPC细胞中，反之亦然。INHBB表达减少可激活TGF-β通路，使Smad 2/3磷酸化并在细胞核中形成复合物，从而导致上述变化。因此，我们的研究结果首次揭示了INHBB可以通过TGF-β信号通路抑制NPC细胞的失巢凋亡抵抗和迁移，降低p53的过表达，并可以作为NPC转移和预后的潜在生物标志物以及治疗应用。
Inhibin B (INHBB), a heterodimer of a common α‐subunit and a βB‐subunit, is a glycoprotein belonging to the transforming growth factor‐β (TGF‐β) family. In this study, we observed INHBB expression was reduced in nasopharyngeal carcinoma (NPC) tissues compared to non‐tumor nasopharyngeal epithelium tissues, and INHBB was associated with lymph node metastasis, stage of disease, and clinical progress. Positive expression of INHBB in NPC predicted a better prognosis (overall survival, P = 0.038). However, the molecular mechanisms of INHBB have not been addressed in NPC. We induced anoikis‐resistant cells in NPC cell lines under anchorage‐independent conditions, then found epithelial‐mesenchymal transition markers changed, cell apoptosis decreased, cell cycle was modified, and invasion strengthened in anoikis‐resistant NPC cells. These anoikis‐resistant NPC cells showed decreased expression of INHBB compared with adhesion cells. Furthermore, INHBB was found to influence the above‐mentioned changes. In the anoikis‐resistant NPC cells with INHBB overexpression, apoptotic cells increased, S phase cells weakened, vimentin, matrix metallopeptidase‐9, and vascular endothelial growth factor A expression were downregulated, and E‐cadherin expression was upregulated, and vice versa in knockdown of INHBB (INHBB shRNA) anoikis‐resistant NPC cells. Diminished INHBB expression could activate the TGF‐β pathway to phosphorylate Smad2/3 and form complexes in the nucleus, which resulted in the above changes. Thus, our results revealed for the first time that INHBB could suppress anoikis resistance and migration of NPC cells by the TGF‐β signaling pathway, decrease p53 overexpression, and could serve as a potential biomarker for NPC metastasis and prognosis as well as a therapeutic application.
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影响因子：
2.9
作者：
Chunhacha P;Sriuranpong V;Chanvorachote P
通讯作者：
Chanvorachote P
影响因子：
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作者：
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影响因子：
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作者：
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通讯作者：
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影响因子：
64.8
作者：
MATZUK, MM;FINEGOLD, MJ;BRADLEY, A
通讯作者：
BRADLEY, A
影响因子：
6.4
作者：
Farkkila, Anniina;Koskela, Sanna;Unkila-Kallio, Leila
通讯作者：
Unkila-Kallio, Leila