当前位置: X-MOL 学术eLife › 论文详情
Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)
MYC and Twist1 cooperate to drive metastasis by eliciting crosstalk between cancer and innate immunity
eLife ( IF 6.4 ) Pub Date : 2020-01-14
Renumathy Dhanasekaran, Virginie Baylot, Minsoon Kim, Sibu Kuruvilla, David I Bellovin, Nia Adeniji, Anand Rajan KD, Ian Lai, Meital Gabay, Ling Tong, Maya Krishnan, Jangho Park, Theodore Hu, Mustafa A Barbhuiya, Andrew J Gentles, Kasthuri Kannan, Phuoc T Tran, Dean W Felsher

Metastasis is a major cause of cancer mortality. We generated an autochthonous transgenic mouse model whereby conditional expression of MYC and Twist1 enables hepatocellular carcinoma (HCC) to metastasize in >90% of mice. MYC and Twist1 cooperate and their sustained expression is required to elicit a transcriptional program associated with the activation of innate immunity, through secretion of a cytokinome that elicits recruitment and polarization of tumor associated macrophages (TAMs). Systemic treatment with Ccl2 and Il13 induced MYC-HCCs to metastasize; whereas, blockade of Ccl2 and Il13 abrogated MYC/Twist1-HCC metastasis. Further, in 33 human cancers (n = 9502) MYC and TWIST1 predict poor survival (p=4.3×10−10), CCL2/IL13 expression (p<10−109) and TAM infiltration (p<10−96). Finally, in the plasma of patients with HCC (n = 25) but not cirrhosis (n = 10), CCL2 and IL13 were increased and IL13 predicted invasive tumors. Therefore, MYC and TWIST1 generally appear to cooperate in human cancer to elicit a cytokinome that enables metastasis through crosstalk between cancer and immune microenvironment.

中文翻译:

MYC和Twist1通过引发癌症与先天免疫之间的串扰来合作推动转移

转移是癌症死亡的主要原因。我们生成了一种自发转基因小鼠模型,其中MYCTwist1的条件表达使肝细胞癌(HCC)在> 90%的小鼠中转移。MYCTwist1协同作用,并需要它们的持续表达来引发与先天免疫激活相关的转录程序,这是通过分泌引起肿瘤相关巨噬细胞(TAM)募集和极化的细胞因子来进行的。用Ccl2和Il13进行全身治疗可诱导MYC -HCC转移。而对Ccl2和Il13的封锁废除了MYC / Twist1-HCC转移。此外,在33例人类癌症(n = 9502)中,MYCTWIST1预测存活率低(p = 4.3×10 -10),CCL2 / IL13表达(p <10 -109)和TAM浸润(p <10 -96)。最后,在肝癌(n = 25)而非肝硬化(n = 10)患者的血浆中,CCL2和IL13升高,IL13预测为浸润性肿瘤。因此,MYCTWIST1通常似乎在人类癌症中协同作用,以引发能够通过癌症与免疫微环境之间的串扰进行转移的细胞因子。
更新日期:2020-01-14
down
wechat
bug