Oncogene：抑制肿瘤细胞转移的新信号通路

2017-01-24 MedSci MedSci原创

促进肿瘤细胞转移的众多信号通路在低/非转移性肿瘤和转移性肿瘤细胞中激活各不相同，这导致转移相关基因的差异表达。而这些差异的潜在机制可能涉及肿瘤细胞中固有负调节的改变。近期，一项发表在Ocogene杂志上的文章报道了白介素-37b（IL-37b）在肿瘤细胞的差异表达改变信号通路的内在负调节，从而导致肿瘤转移能力的差异。 IL-37b可以通过干扰Smad2 / 3/4复合物的形成和核易位来结

促进肿瘤细胞转移的众多信号通路在低/非转移性肿瘤和转移性肿瘤细胞中激活各不相同，这导致转移相关基因的差异表达。而这些差异的潜在机制可能涉及肿瘤细胞中固有负调节的改变。

近期，一项发表在Ocogene杂志上的文章报道了白介素-37b（IL-37b）在肿瘤细胞的差异表达改变信号通路的内在负调节，从而导致肿瘤转移能力的差异。

IL-37b可以通过干扰Smad2 / 3/4复合物的形成和核易位来结合Smad3并抑制Smad通路。反过来，Smad3可以作为共调节器，使IL-37b抑制多个非Smad途径。

IL-37b-Smad3转位到细胞核中可以上调非受体蛋白酪氨酸磷酸酶（PTPNs）的表达，从而促进去磷酸化以抑制酪氨酸磷酸化依赖性信号通路的活化，如ERK，p38 MAPK，JNK，PI3K，NF- κB和STAT3通路。

有趣的是，由于IL-37b的低表达导致17个PTPN中有13个（其中大多数是转移抑制子）在转移性肿瘤细胞中被下调。细胞内IL-37b的显着减少削弱了肿瘤细胞中的内在负调节，导致多个信号通路的增强的活化并增加的肿瘤细胞的侵袭能力和转移定植的能力。

于此相一致的是IL-37b在肿瘤中的低表达与癌症患者的不良预后显着相关。

总之，此项研究结果显示，细胞内IL-37b是调节肿瘤转移相关基因表达的多种信号途径的负调节中的关键因素，并且表明IL-37b在肿瘤细胞中的表达可能是组织病理学预后的参数，其可用于癌症患者预防肿瘤转移的治疗靶标。

原始出处：
Luo C, Shu Y, Luo J, et al.Intracellular IL-37b interacts with Smad3 to suppress multiple signaling pathways and the metastatic phenotype of tumor cells.Oncogene. 2017 Jan 16. doi: 10.1038/onc.2016.444.

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2017-02-09 cy0324

#Gene#

156 0
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2017-03-30 xiaoyang_ambs

#抑制肿瘤#

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2017-01-26 hmwwww

#肿瘤细胞#

81 0
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2017-01-26 zz72

#细胞转移#

79 0
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2017-01-26 wgx310

#信号通路#

87 0
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2017-01-26 zsyan

#Oncogene#

99 0
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2017-01-25 doctorJiangchao

继续学习

119 0
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2017-01-25 1dd8aa01m06(暂无匿称)

学习了，很好的内容

129 0
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2017-01-24 knowheart

很好的学习资料

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