Twisted Gastrulation BMP Signaling Modulator 1 Regulates Papillary Thyroid Cancer Cell Motility and Proliferation.
Twisted Gastrulation BMP Signaling Modulator 1 Regulates Papillary Thyroid Cancer Cell Motility and Proliferation.
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扭曲原肠胚形成 BMP 信号调节剂 1 调节甲状腺乳头状癌细胞的运动和增殖
DOI：
10.7150/jca.18482
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发表时间：
2017
影响因子：
3.9
通讯作者：
Zhan W
中科院分区：
文献类型：
--
作者：
Xia S;Ji R;Xu Y;Ni X;Dong Y;Zhan W
骨形态发生蛋白（Bone morphogenetic proteins, BMPs）是一种生长因子，在细胞增殖、迁移和分化过程中具有重要的功能。迄今为止，BMP通路的激活已在多种人类肿瘤中发现，并与恶性肿瘤的生长和转移增强有关。BMP活性受到一系列可溶性细胞外分泌BMP调节剂的严格调控。扭曲原肠胚BMP信号调节因子1 （TWSG1）是BMP全部信号活动所必需的直接BMP调节因子。然而，TWSG1在甲状腺乳头状癌（PTC）转移中的作用和机制尚未见报道。采用实时荧光定量聚合酶链反应（qRT-PCR）检测TWSG1在44例淋巴结转移（LNM）和56例无淋巴结转移的PTC组织中的表达。使用功能增益和功能丧失方法来评估PTC细胞中TWSG1的生物学功能。基质分析证实了肿瘤细胞来源的TWSG1对内皮细胞功能的影响。我们的研究结果显示，与未进行LNM的PTC相比，有LNM的PTC中TWSG1的表达显著增强。敲低TWSG1可抑制PTC细胞的迁移、侵袭和增殖。此外，TWSG1抑制抑制了肿瘤细胞诱导的内皮细胞芽的形成。我们发现TWSG1信号可能由BMP靶转录因子DNA结合抑制因子1 （Id1）和基质金属蛋白酶（MMPs） 2和9转导。综上所述，TWSG1在转移性PTC中高表达；肿瘤的生长、迁移和侵袭均依赖于TWSG1，可能成为PTC新的诊断和治疗靶点。
Bone morphogenetic proteins (BMPs) are growth factors that have important functions in cell proliferation, migration and differentiation. To date, BMP pathway activation has been found in multiple human tumors and is associated with enhanced malignant tumor growth and metastasis. BMP activity is tightly regulated by a family of soluble extracellular secreted BMP modulators. Twisted gastrulation BMP signaling modulator 1 (TWSG1) is a direct BMP regulator that is required for the full signaling activity of BMPs. However, the functions and mechanisms of TWSG1 in papillary thyroid cancer (PTC) metastasis have not been reported. TWSG1 expression was detected in 44 PTC tissues with lymph node metastasis (LNM) and 56 PTC tissues without LNM using quantitative real-time polymerase chain reaction (qRT-PCR). Gain- and loss-of-function approaches were used to assess the biological function of TWSG1 in PTC cells. Matrigel assays demonstrated the effect of tumor cell-derived TWSG1 on endothelial cell function. Our results showed that TWSG1 expression was significantly enhanced in PTC with LNM compared to that in PTC without LNM. TWSG1 knockdown inhibited migration, invasion and proliferation of PTC cells. Additionally, TWSG1 suppression impaired the tumor cell-induced endothelial cell sprout formation. We found that TWSG1 signaling may be transduced by the BMP target transcription factor inhibitor of DNA binding 1 (Id1) and matrix metalloproteinases (MMPs) 2 and 9. In conclusion, TWSG1 was highly expressed in metastasized PTC; tumor growth, migration and invasion were dependent on TWSG1, and it may be a new diagnostic and therapeutic target for PTC.
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影响因子：
3.7
作者：
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通讯作者：
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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：
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作者：
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