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：

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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MYC和Twist1的条件表达使肝细胞癌（HCC）在> 90％的小鼠中转移。MYC和Twist1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，MYC和TWIST1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，MYC和TWIST1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。